bims-flamet Biomed News
on Cytokines and immunometabolism in metastasis
Issue of 2025–03–23
thirty-one papers selected by
Peio Azcoaga, Biodonostia HRI
  1. Recent advances in the mechanisms of PD-L1 expression in gastric cancer: a review.
  2. Contribution of tumor microenvironment (TME) to tumor apoptosis, angiogenesis, metastasis, and drug resistance.
  3. Mechanisms of tumor-associated macrophages in breast cancer and treatment strategy.
  4. The tumor microenvironment is an ecosystem sustained by metabolic interactions.
  5. Significance of PAI-1 on the development of skin cancer: optimal targets for cancer therapies.
  6. Parallels in Canonical Developmental Signaling Pathways between Normal Development and the Tumor Microenvironment.
  7. Tumor suppressor genes in the tumor microenvironment.
  8. Targeting myeloid-derived suppressor cells in the tumor microenvironment: potential therapeutic approaches for osteosarcoma.
  9. Metabolic mechanisms of immunotherapy resistance.
  10. Cancer‑associated fibroblasts: a pivotal regulator of tumor microenvironment in the context of radiotherapy.
  11. Resveratrol and pancreatic cancers: Questions and future perspectives.
  12. Tumor microenvironment: recent advances in understanding and its role in modulating cancer therapies.
  13. Tumor-derived extracellular vesicles: key drivers of immunomodulation in breast cancer.
  14. Cancer-associated fibroblasts in ovarian cancer: research progress.
  15. Tumoricidal potential of binary therapy in lymphoma: Role of DC-NK cross-talk and checkpoint inhibitors.
  16. The role of type I interferon signaling in myeloid anti-tumor immunity.
  17. Reprogramming tumor-associated macrophages in gastric cancer: a pathway to enhanced immunotherapy.
  18. Asporin increases the extracellular matrix cross-links and inhibits the cancer cell migration.
  19. The combination of Shenhuang plaster and paclitaxel inhibits lung metastasis in breast cancer via modulation of the tumor microenvironment.
  20. Advances in imaging techniques for tumor microenvironment evaluation in hepatocellular carcinoma.
  21. New insights on anti-tumor immunity of CD8+ T cells: cancer stem cells, tumor immune microenvironment and immunotherapy.
  22. Adoptive cell therapy against tumor immune evasion: mechanisms, innovations, and future directions.
  23. Senescence-associated secretory phenotype regulation by dual-drug delivery biomimetic nanoplatform for enhanced tumor chemotherapy.
  24. Targeting novel immune checkpoints in the B7-H family: advancing cancer immunotherapy from bench to bedside.
  25. Impacts of combining PD-L1 inhibitor and radiotherapy on the tumour immune microenvironment in a mouse model of esophageal squamous cell carcinoma.
  26. CD44-Targeted nanoparticles for remodeling the tumor microenvironment in a 3D Macrophage-Embedded ovarian cancer model with stem Cell-Like features.
  27. CD24-targeted CAR-T cells mediated long-term anti-tumor efficacy through activation of endogenous tumor immune responses.
  28. Neutrophils in colorectal cancer: mechanisms, prognostic value, and therapeutic implications.
  29. SNHG family lncRNAs: key players in the breast cancer progression and immune cell's modulation.
  30. Extracellular vesicles in cancer´s communication: messages we can read and how to answer.
  31. CD38-mediated metabolic reprogramming promotes the stability and suppressive function of regulatory T cells in tumor.
  1. Biol Res. 2025 Mar 17. 58(1): 16
    Recent advances in the mechanisms of PD-L1 expression in gastric cancer: a review.
    Peifeng Chen, Zhangming Chen, Wannian Sui, Wenxiu Han.
      In the progression of gastric cancer (GC), various cell types in the tumor microenvironment (TME) exhibit upregulated expression of programmed death ligand 1 (PD-L1), leading to impaired T-cell function and evasion of immune surveillance. Infection with H. pylori and EBV leads to increased PD-L1 expression in various cell types within TME, resulting in immune suppression and facilitating immune escape of GC cells. In the TME, mesenchymal stem cells (MSCs), M1-like tumor-associated macrophages (MI-like TAM), and myeloid-derived suppressor cells (MDSCs) contribute to the upregulation of PD-L1 expression in GC cells. Conversely, mast cells, M2-like tumor-associated macrophages (M2-like TAM), and tumor-associated neutrophils (TANs) exhibit elevated levels of PD-L1 expression in response to the influence of GC cells. Together, these factors collectively contribute to the upregulation of PD-L1 expression in GC. This review aims to provide a comprehensive summary of the cellular expression patterns of PD-L1 in GC and the underlying molecular mechanisms. Understanding the complex regulatory pathways governing PD-L1 expression may offer novel insights for the development of effective immunotherapeutic interventions.
    Keywords:  Gastric cancer; Programmed death ligand 1; Tumor immunity; Tumor microenvironment
    DOI:  https://doi.org/10.1186/s40659-025-00597-3
  2. Med Oncol. 2025 Mar 14. 42(4): 108
    Contribution of tumor microenvironment (TME) to tumor apoptosis, angiogenesis, metastasis, and drug resistance.
    Yanhong Xiao, Mahan Hassani, Melina Barahouei Moghaddam, Ahmad Fazilat, Masoud Ojarudi, Mohammad Valilo.
      The tumor microenvironment (TME) contains tumor cells, surrounding cells, and secreted factors. It provides a favorable environment for the maintenance of cancer stem cells (CSCs), the spread of cancer cells to metastatic sites, angiogenesis, and apoptosis, as well as the growth, proliferation, invasion, and drug resistance of cancer cells. Cancer cells rely on the activation of oncogenes, inactivation of tumor suppressors, and the support of a normal stroma for their growth, proliferation, and survival, all of which are provided by the TME. The TME is characterized by the presence of various cells, including cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), CD8 + cytotoxic T cells (CTLs), regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), mesenchymal stem cells (MSCs), endothelial cells, adipocytes, and neuroendocrine (NE) cells. The high expression of inflammatory cytokines, angiogenic factors, and anti-apoptotic factors, as well as drug resistance mechanisms in the TME, contributes to the poor therapeutic efficacy of anticancer drugs and tumor progression. Hence, this review describes the mechanisms through which the TME is involved in apoptosis, angiogenesis, metastasis, and drug resistance in tumor cells.
    Keywords:  Angiogenesis; Apoptosis; Drug resistance; Metastasis; Tumor microenvironment
    DOI:  https://doi.org/10.1007/s12032-025-02675-8
  3. Front Immunol. 2025 ;16 1560393
    Mechanisms of tumor-associated macrophages in breast cancer and treatment strategy.
    Hong Jin, Xinyue Meng, Jianwei Feng.
      Breast cancer (BC) is the most common cancer in women and a leading cause of cancer-related mortality. Despite advances in screening and treatment, outcomes for advanced or recurrent BC remain poor, highlighting the need for new strategies. Recent research emphasizes the tumor microenvironment (TME), particularly tumor-associated macrophages (TAMs), as key drivers of tumor growth, metastasis, and resistance to therapy. The presence of M2-like TAMs in the TME promotes immune evasion and tumor progression across BC subtypes. This review summarizes TAMs classification, their role in BC, and emerging therapies targeting TAMs, including depletion, inhibition of recruitment, and reprogramming from pro-tumoral M2 to anti-tumoral M1 phenotypes. Targeting TAMs offers a promising strategy to improve BC treatment outcomes.
    Keywords:  HER2; TAMs; breast cancer; macrophages; treatment; tumor microenvironment
    DOI:  https://doi.org/10.3389/fimmu.2025.1560393
  4. Cell Rep. 2025 Mar 13. pii: S2211-1247(25)00203-7. [Epub ahead of print]44(3): 115432
    The tumor microenvironment is an ecosystem sustained by metabolic interactions.
    Emily Jane Kay, Sara Zanivan.
      Cancer-associated fibroblasts (CAFs) and immune cells make up two major components of the tumor microenvironment (TME), contributing to an ecosystem that can either support or restrain cancer progression. Metabolism is a key regulator of the TME, providing a means for cells to communicate with and influence each other, modulating tumor progression and anti-tumor immunity. Cells of the TME can metabolically interact directly through metabolite secretion and consumption or by influencing other aspects of the TME that, in turn, stimulate metabolic rewiring in target cells. Recent advances in understanding the subtypes and plasticity of cells in the TME both open up new avenues and create challenges for metabolically targeting the TME to hamper tumor growth and improve response to therapy. This perspective explores ways in which the CAF and immune components of the TME could metabolically influence each other, based on current knowledge of their metabolic states, interactions, and subpopulations.
    Keywords:  CAFs; CP: Cancer; CP: Metabolism; immune cells; metabolism; stroma immune; tumor microenvironment
    DOI:  https://doi.org/10.1016/j.celrep.2025.115432
  5. Biomed J. 2025 Mar 18. pii: S2319-4170(25)00024-1. [Epub ahead of print] 100850
    Significance of PAI-1 on the development of skin cancer: optimal targets for cancer therapies.
    Taku Fujimura.
      Plasminogen activator inhibitor-1 (PAI-1) is a serine protease inhibitor that plays a critical role in cancer progression, particularly in skin cancers. PAI-1 is widely recognized for its role in inhibiting fibrinolysis; however, emerging evidence suggests that it also contributes to tumor progression through multiple mechanisms, including tumor angiogenesis, immunomodulation, and stromal cell regulation. In the tumor microenvironment (TME), PAI-1 influences tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs), promoting an immunosuppressive environment that supports cancer growth and therapy resistance. Furthermore, PAI-1 has been implicated in the regulation of programmed death-ligand 1 (PD-L1) expression via the JAK/STAT signaling pathway, thereby influencing immune evasion in various skin cancers. The significance of PAI-1 as a therapeutic target has been demonstrated in melanoma and other cutaneous malignancies, where inhibition of PAI-1 has shown promise in overcoming resistance to immune checkpoint inhibitors. Additionally, clinical trials evaluating PAI-1 inhibitors, such as TM5614, highlight its potential as an adjunctive therapy for melanoma and cutaneous angiosarcoma. This review comprehensively explores PAI-1's role in skin cancer progression, its influence on tumor-stromal interactions, and its potential as a therapeutic target.
    Keywords:  PAI-1; angiogenesis; cancer-associated fibroblasts; immune checkpoint inhibitors; immunotherapy; skin cancer; tumor microenvironment; tumor-associated macrophages
    DOI:  https://doi.org/10.1016/j.bj.2025.100850
  6. Cold Spring Harb Perspect Med. 2025 Mar 17. pii: a041609. [Epub ahead of print]
    Parallels in Canonical Developmental Signaling Pathways between Normal Development and the Tumor Microenvironment.
    Julia Segal, James Cronk, Brendan Ball, Greta Forbes, Kailey Jackett, Kathy Li, Alondra Martinez Osorno, Emily San Andres Montalvan, Alice Browne, Jessica Lake, Rosandra N Kaplan.
      The tumor microenvironment (TME) is comprised of both cellular and stromal elements and plays an essential role in the growth, survival, and dissemination of malignancies. The TME is an organized program that develops with a growing tumor, using many processes involved in normal tissue development. In multiple solid tumors, developmental pathways are used to recruit immunosuppressive cells, including immunosuppressive monocytes and neutrophils, tumor-associated macrophages, and regulatory T cells to block the antitumor immune response. In addition, stromal cells sustain tumor growth via trophic support, angiogenesis, repair mechanisms, and associated immunosuppression, driven, at least in part, by canonical developmental signaling pathways. The microenvironmental ecosystem shapes tumor progression from its earliest inception by modulating important programs that dictate tumor behavior, necessitating further consideration when studying the developmental origins of malignancy. Here, we review the role of developmental pathways in the formation and modulation of the TME in pediatric and adult solid tumors, including Wnt, Notch, Hippo, Hedgehog, TGF-β, BMP, SOX, and OCT.
    DOI:  https://doi.org/10.1101/cshperspect.a041609
  7. Dis Model Mech. 2025 Mar 01. pii: dmm052049. [Epub ahead of print]18(3):
    Tumor suppressor genes in the tumor microenvironment.
    Bahareh Tabanifar, Hannah Lau, Kanaga Sabapathy.
      Tumor suppressor genes (TSGs) are thought to suppress tumor development primarily via cancer cell-autonomous mechanisms. However, the tumor microenvironment (TME) also significantly influences tumorigenesis. In this context, a role for TSGs in the various cell types of the TME in regulating tumor growth is emerging. Indeed, expression analyses of TSGs in clinical samples, along with data from mouse models in which TSGs were deleted selectively in the TME, indicate a functional role for them in tumor development. In this Perspective, using TP53 and PTEN as examples, we posit that TSGs play a significant role in cells of the TME in regulating tumor development, and postulate both a 'pro-active' and 'reactive' model for their contribution to tumor growth, dependent on the temporal sequence of initiating events. Finally, we discuss the need to consider a 2-in-1 cancer-treatment strategy to improve the efficacy of clearance of cancer cells and the cancer-promoting TME.
    Keywords:  Fibroblasts; PTEN; TP53; Tumor microenvironment; Tumor suppressors
    DOI:  https://doi.org/10.1242/dmm.052049
  8. Oncol Res. 2025 ;33(3): 519-531
    Targeting myeloid-derived suppressor cells in the tumor microenvironment: potential therapeutic approaches for osteosarcoma.
    Hye In Ka, Se Hwan Mun, Sora Han, Young Yang.
      Osteosarcoma is a bone malignancy characterized by strong invasiveness and rapid disease progression. The tumor microenvironment of osteosarcoma contains various types of immune cells, including myeloid-derived suppressor cells, macrophages, T cells, and B cells. Imbalances of these immune cells can promote the proliferation and metastasis of osteosarcoma. Recent studies have indicated a substantial increase in the levels of myeloid-derived suppressor cells, an immune cell associated with immunosuppressive and pro-cancer effects, in the peripheral blood of patients with osteosarcoma. Moreover, the levels of the pro-inflammatory cytokine interleukin 18 are positively correlated with those of myeloid-derived suppressor cells in the peripheral blood of animal models of osteosarcoma. In this review, we explore the function of myeloid-derived suppressor cells in osteosarcoma based on the clinical diagnoses of patients with osteosarcoma and discuss future therapeutic approaches for targeting osteosarcoma. Targeting myeloid-derived suppressor cells represents a promising approach to improving the prognosis and survival rates of patients with osteosarcoma.
    Keywords:  Bone malignancy; Immune cells; Myeloid-derived suppressor cells (MDSC); Tumor microenvironment (TME)
    DOI:  https://doi.org/10.32604/or.2024.056860
  9. Explor Target Antitumor Ther. 2025 ;6 1002297
    Metabolic mechanisms of immunotherapy resistance.
    Luis Cabezón-Gutiérrez, Magda Palka-Kotlowska, Sara Custodio-Cabello, Beatriz Chacón-Ovejero, Vilma Pacheco-Barcia.
      Immunotherapy has revolutionized cancer treatment, yet its efficacy is frequently compromised by metabolic mechanisms that drive resistance. Understanding how tumor metabolism shapes the immune microenvironment is essential for developing effective therapeutic strategies. This review examines key metabolic pathways influencing immunotherapy resistance, including glucose, lipid, and amino acid metabolism. We discuss their impact on immune cell function and tumor progression, highlighting emerging therapeutic strategies to counteract these effects. Tumor cells undergo metabolic reprogramming to sustain proliferation, altering the availability of essential nutrients and generating toxic byproducts that impair cytotoxic T lymphocytes (CTLs) and natural killer (NK) cell activity. The accumulation of lactate, deregulated lipid metabolism, and amino acid depletion contribute to an immunosuppressive tumor microenvironment (TME). Targeting metabolic pathways, such as inhibiting glycolysis, modulating lipid metabolism, and restoring amino acid balance, has shown promise in enhancing immunotherapy response. Addressing metabolic barriers is crucial to overcoming immunotherapy resistance. Integrating metabolic-targeted therapies with immune checkpoint inhibitors may improve clinical outcomes. Future research should focus on personalized strategies to optimize metabolic interventions and enhance antitumor immunity.
    Keywords:  Immune resistance; cancer; metabolism; tumor microenvironment
    DOI:  https://doi.org/10.37349/etat.2025.1002297
  10. Cell Commun Signal. 2025 Mar 20. 23(1): 147
    Cancer‑associated fibroblasts: a pivotal regulator of tumor microenvironment in the context of radiotherapy.
    Linhui Zheng, Wenqi Cai, Yuan Ke, Xiaoyan Hu, Chunqian Yang, Runze Zhang, Huachao Wu, Dong Liu, Haijun Yu, Chaoyan Wu.
       BACKGROUND: In the course of tumor treatment, radiation therapy (RT) not only kills cancer cells, but also induces complex biological effects in non-malignant cells around cancer cells. These biological effects such as angiogenesis, changes in stromal composition and immune cell infiltration remodel the tumor microenvironment (TME). As one of the major components of the TME, Cancer‑associated fibroblasts (CAFs) are not only involved in tumorigenesis, progression, recurrence, and metastasis but also regulate the tumor-associated immune microenvironment. CAFs and tumor cells or immune cells have complex intercellular communication in the context of tumor radiation.
    MAIN CONTENT: Different cellular precursors, spatial location differences, absence of specific markers, and advances in single-cell sequencing technology have gradually made the abundant heterogeneity of CAFs well known. Due to unique radioresistance properties, CAFs can survive under high doses of ionizing radiation. However, radiation can induce phenotypic and functional changes in CAFs and further act on tumor cells and immune cells to promote or inhibit tumor progression. To date, the effect of RT on CAFs and the effect of irradiated CAFs on tumor progression and TME are still not well defined.
    CONCLUSION: In this review, we review the origin, phenotypic, and functional heterogeneity of CAFs and describe the effects of RT on CAFs, focusing on the mutual crosstalk between CAFs and tumor or immune cells after radiation. We also discuss emerging strategies for targeted CAFs therapy.
    Keywords:  Cancer associated fibroblast; Immune microenvironment; Radiation therapy; Tumor microenvironment
    DOI:  https://doi.org/10.1186/s12964-025-02138-7
  11. World J Gastrointest Oncol. 2025 Mar 15. 17(3): 100342
    Resveratrol and pancreatic cancers: Questions and future perspectives.
    Olga A Sukocheva.
      There is still no effective treatment for pancreatic cancer, one of the deadliest malignancies among the gastrointestinal diseases. Jiang et al demonstrated the presence of senescent cancer-associated fibroblasts (CAFs) in pancreatic cancer tissues, supporting the use of CAFs as potential anti-cancer targets. The study indicated that a natural plant-derived compound resveratrol can reverse senescent CAF phenotype and decrease the growth, migration, and invasiveness of pancreatic cancer cells. Notably, the study indicated that resveratrol might be involved in regulating epithelial-to-mesenchymal transition in the tumor microenvironment. This editorial shares insights on the future investigation of resveratrol signaling in cancer cells and the tumor microenvironment, and discusses resveratrol-based treatment perspectives.
    Keywords:  Antioxidant; Cancer-associated fibroblasts; Immune senescence; Pancreatic cancer; Resveratrol; Tumor microenvironment
    DOI:  https://doi.org/10.4251/wjgo.v17.i3.100342
  12. Med Oncol. 2025 Mar 18. 42(4): 117
    Tumor microenvironment: recent advances in understanding and its role in modulating cancer therapies.
    Disha D Shah, Mehul R Chorawala, Neha R Raghani, Rajanikant Patel, Mohammad Fareed, Vivekanand A Kashid, Bhupendra G Prajapati.
      Tumor microenvironment (TME) denotes the non-cancerous cells and components presented in the tumor, including molecules produced and released by them. Interactions between cancer cells, immune cells, stromal cells, and the extracellular matrix within the TME create a dynamic ecosystem that can either promote or hinder tumor growth and spread. The TME plays a pivotal role in either promoting or inhibiting tumor growth and dissemination, making it a critical factor to consider in the development of effective cancer therapies. Understanding the intricate interplay within the TME is crucial for devising effective cancer therapies. Combination therapies involving inhibitors of immune checkpoint blockade (ICB), and/or chemotherapy now offer new approaches for cancer therapy. However, it remains uncertain how to best utilize these strategies in the context of the complex tumor microenvironment. Oncogene-driven changes in tumor cell metabolism can impact the TME to limit immune responses and present barriers to cancer therapy. Cellular and acellular components in tumor microenvironment can reprogram tumor initiation, growth, invasion, metastasis, and response to therapies. Components in the TME can reprogram tumor behavior and influence responses to treatments, facilitating immune evasion, nutrient deprivation, and therapeutic resistance. Moreover, the TME can influence angiogenesis, promoting the formation of blood vessels that sustain tumor growth. Notably, the TME facilitates immune evasion, establishes a nutrient-deprived milieu, and induces therapeutic resistance, hindering treatment efficacy. A paradigm shift from a cancer-centric model to a TME-centric one has revolutionized cancer research and treatment. However, effectively targeting specific cells or pathways within the TME remains a challenge, as the complexity of the TME poses hurdles in designing precise and effective therapies. This review highlights challenges in targeting the tumor microenvironment to achieve therapeutic efficacy; explore new approaches and technologies to better decipher the tumor microenvironment; and discuss strategies to intervene in the tumor microenvironment and maximize therapeutic benefits.
    Keywords:  Cancer therapies; Combination therapies; Immune checkpoint inhibitors; Nanomedicine; Nutrient-deprived environment; Therapeutic resistance; Tumor microenvironment (TME)
    DOI:  https://doi.org/10.1007/s12032-025-02641-4
  13. Front Immunol. 2025 ;16 1548535
    Tumor-derived extracellular vesicles: key drivers of immunomodulation in breast cancer.
    Jieming Li, Shuo Yu, Min Rao, Bomin Cheng.
      Breast cancer (BC) remains a significant global health challenge characterized by its heterogeneity and treatment complexities. Extracellular vesicles (EVs) are small membranous particles released by cells, facilitating intercellular communication by transporting bioactive molecules such as proteins, lipids, and nucleic acids. Tumor-derived EVs have emerged as pivotal regulators in the tumor microenvironment (TME) and drivers of BC progression. These EVs carry diverse cargoes of bioactive molecules, influencing critical processes such as immune modulation, angiogenesis, and metastasis. By altering the behaviors of immune cells including macrophages, dendritic cells, and T cells, tumor-derived EVs contribute to immune evasion and tumor growth. Furthermore, Tumor-derived EVs play a role in mediating drug resistance, impacting the effectiveness of therapeutic interventions. Understanding the multifaceted roles of BC tumor-derived EVs is essential for the development of innovative therapeutic strategies. Targeting pathways mediated by EVs holds promise for enhancing the efficacy of cancer treatments and improving patient outcomes. This comprehensive review provides insights into the intricate interactions of tumor-derived EVs in immune modulation and BC progression, highlighting potential therapeutic targets and avenues for novel cancer therapies.
    Keywords:  T cells; breast cancer; extracellular vesicles; immune regulation; macrophages
    DOI:  https://doi.org/10.3389/fimmu.2025.1548535
  14. Front Oncol. 2025 ;15 1504762
    Cancer-associated fibroblasts in ovarian cancer: research progress.
    Yuance Xu, Danting Sun, Junqi He, Qin Yao.
      Ovarian cancer, known for its high invasiveness and therapeutic resistance, is one of the leading causes of death from gynecological tumors. The tumor microenvironment (TME) plays a crucial role in the development of ovarian cancer, with cancer-associated fibroblasts (CAFs) being a key non-tumor cell component. They significantly affect the prognosis of ovarian cancer by promoting tumor cell proliferation, invasion, metastasis, immune evasion, and drug resistance. The heterogeneity of CAFs provides a new perspective for targeted therapy in ovarian cancer. This review comprehensively analyzes the mechanisms of action, heterogeneity characteristics, and role in the immune microenvironment of CAFs in ovarian cancer, and discusses targeted therapy strategies for CAFs, aiming to provide new theoretical basis and treatment directions for the treatment of ovarian cancer.
    Keywords:  cancer-associated fibroblasts (CAFs); immune microenvironment; ovarian cancer; targeted therapy; tumor microenvironment
    DOI:  https://doi.org/10.3389/fonc.2025.1504762
  15. Histol Histopathol. 2025 Mar 07. 18900
    Tumoricidal potential of binary therapy in lymphoma: Role of DC-NK cross-talk and checkpoint inhibitors.
    Pratima Chaudhary, Pragya Yadav, Partha Pratim Manna.
      Lymphoma is a common type of cancer that occurs in humans. Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma (NHL) subtype and is characterized by high clinical and biological heterogeneity. The tumor microenvironment (TME) in lymphoma is critical for the initiation, progression, and metastasis of tumors and influences the therapeutic efficiency of chemotherapy or immunotherapy, including cell therapy or appropriate combinations of therapeutics. The role of effector immune cells in the development and progression of DLBCL is complex and involves reciprocal interactions between tumor cells, adaptive and innate immune cells, their soluble mediators, and structural components present in the TME. Recruitment of immune cells in the TME and their distinct effects on tumor progression and therapeutic outcomes in the presence of therapy have decisive effects on the outcome of therapy. In this review, we discuss the application and implications of binary therapy involving suboptimal-dose chemotherapy and adoptive cell therapy on the basis of our recent findings on γc cytokine-aided cross-talk between dendritic cells and natural killer cells in therapy against experimental murine lymphoma. This novel therapeutic protocol induces a healing response in experimental lymphoma by downregulating FOXP3 and programmed cell death protein 1. We discuss the various aspects of binary therapy covering multiple issues, including the participation of cell subsets and checkpoint inhibitors in the treatment of malignant lymphoma. These new therapies involve the induction of adoptive cell therapy through the passive transfer of immunologic effectors in addition to a suboptimal dose of adriamycin (doxorubicin hydrochloride) to increase the ability of the immune system to react against tumor antigens, inducing the destruction of tumor cells.
    DOI:  https://doi.org/10.14670/HH-18-900
  16. Front Immunol. 2025 ;16 1547466
    The role of type I interferon signaling in myeloid anti-tumor immunity.
    Sofie Patrizia Meyer, Rebekka Bauer, Bernhard Brüne, Tobias Schmid.
      Tumors often arise in chronically inflamed, and thus immunologically highly active niches. While immune cells are able to recognize and remove transformed cells, tumors eventually escape the control of the immune system by shaping their immediate microenvironment. In this context, macrophages are of major importance, as they initially exert anti-tumor functions before they adopt a tumor-associated phenotype that instead inhibits anti-tumor immune responses and even allows for sustaining a smoldering inflammatory, growth promoting tumor microenvironment (TME). Type I interferons (IFNs) are well established modulators of inflammatory reactions. While they have been shown to directly inhibit tumor growth, there is accumulating evidence that they also play an important role in altering immune cell functions within the TME. In the present review, we focus on the impact of type I IFNs on anti-tumor responses, driven by monocytes and macrophages. Specifically, we will provide an overview of tumor-intrinsic factors, which impinge on IFN-stimulated gene (ISG) expression, like the presence of nucleic acids, metabolites, or hypoxia. We will further summarize the current understanding of the consequences of altered IFN responses on macrophage phenotypes, i.e., differentiation, polarization, and functions. For the latter, we will focus on macrophage-mediated tumor cell killing and phagocytosis, as well as on how macrophages affect their environment by secreting cytokines and directly interacting with immune cells. Finally, we will discuss how type I IFN responses in macrophages might affect and should be considered for current and future tumor therapies.
    Keywords:  hypoxia; macrophage; phagocytosis; polarization; tumor microenvironment; type I interferon
    DOI:  https://doi.org/10.3389/fimmu.2025.1547466
  17. Front Immunol. 2025 ;16 1558091
    Reprogramming tumor-associated macrophages in gastric cancer: a pathway to enhanced immunotherapy.
    Yibo He, Qianran Hong, Shiliang Chen, Jiayi Zhou, Shengliang Qiu.
      Gastric cancer (GC) remains a significant global health concern due to its poor prognosis and limited therapeutic options, particularly in advanced stages. Tumor microenvironment (TME), particularly tumor-associated macrophages (TAMs), plays a key role in tumor progression, immune evasion, and therapy resistance. TAMs exhibit plasticity, shifting between pro-inflammatory M1 and immunosuppressive M2 phenotypes, with the latter predominating in GC and contributing to poor outcomes. Recent therapeutic advancements focus on targeting TAMs, including inhibiting M2 polarization, reprogramming TAMs to M1 phenotypes, and combining TAM-targeted approaches with immune checkpoint inhibitors. Innovations in nanotechnology, metabolic reprogramming, and targeting key pathways such as interleukin-6 and C-C motif ligand 2/C-C motif chemokine receptor 2 further enhance these strategies. However, challenges remain, including the spatial and functional heterogeneity of TAMs within the TME and the need for selective targeting to avoid disrupting immune homeostasis. Ongoing research on TAM origins, functions, and interactions within the TME is crucial for developing precise and effective therapies. These advances hold promise not only for improving outcomes in GC but also for addressing other cancers with similarly complex microenvironments.
    Keywords:  gastric cancer; immunotherapy; polarization of macrophages; tumor microenvironment; tumor-associated macrophages
    DOI:  https://doi.org/10.3389/fimmu.2025.1558091
  18. Tumour Biol. 2025 Jan-Dec;47:47 10104283241313441
    Asporin increases the extracellular matrix cross-links and inhibits the cancer cell migration.
    Kimberly Hernandez, Caitlin H Nguyen, Girdhari Rijal.
      BackgroundMigrating strategies of the triple-negative breast cancer (TNBC) together with its role in the establishment of tumor microenvironment (TME), supporting metastasis, have been extensively studied. Extracellular matrix (ECM) is a major player for the TME, establishing the 3D spatial networks with interconnected pores necessary for the mechano-physiological function of the cells. Certain collagen aligners and cross-linkers which are necessary for the formation and the stabilization of ECM networks, however, have not been studied either in normal or in abnormal tissues. Complexities in cell-cell and cell-matrix interactions, and different in types and ratios of ECM proteins in a TME challenge to reveal the precise function of a particular protein that is exhibited by special cells and if specifically present in insignificant amount. Cancer-associated fibroblasts (CAFs) predominantly occupy the major stroma of a solid tumor where they deposit extracellular proteins in the excessive amount compared to other tumor-associated cells. For example, the TNBC tumor itself is positive for asporin (ASPN) since CAFs are major ASPN exhibitors. However, the TNBC cells express it insignificantly.ObjectiveThe increase in ECM and its networks suppresses the metastasis.MethodsHere, we studied the expression of collagen type I and ASPN in CAFS and MDA-MB-231 (MM231), and evaluated the role of ASPN in collagen alignment and crosslinking.ResultsTNBC cells have an insignificant expression of ASPN and scanty collagen fibers, some of which aggregate to form the stiff deranged fibers, forming large-size pores in ECM of cancer-cell-dominant outer core of TNBC that support cancer cell invasion and metastasis. Exogenous ASPN and fibroblast-ASPN supported for the collagen alignment and crosslinking that established the small-size pores in the ECM, inhibiting the cancer cell invasion.ConclusionsThe collagen aligner and the cross-linker, ASPN increases the ECM networks and decreases the migration, and this preliminary study provides the hope that ASPN might be used as an anti-metastatic drug after its confirmation through extensive studies in animal, and positive outcomes through preclinical trials.
    Keywords:  ASPN; CAF; MDA-MB-231; collagen; extracellular matrix; metastasis; tumor microenvironment
    DOI:  https://doi.org/10.1177/10104283241313441
  19. Front Oncol. 2025 ;15 1531493
    The combination of Shenhuang plaster and paclitaxel inhibits lung metastasis in breast cancer via modulation of the tumor microenvironment.
    Shiqi Chen, Maryam Mohammed Abbas Karekad, Ting Liu, Bin Ding, Rongyun Wang, Qiuhua Sun, Xiaohong Xu, Yanan Shi.
       Background: Paclitaxel (PTX) is a chemotherapeutic agent that is frequently used for breast cancer treatment, but it has been associated with promoting distant metastases, including to the lungs, liver, and bones. Shenhuang plaster (SHP), a traditional Chinese medicine, has shown potential for modulating the tumor microenvironment (TME). This study investigates whether a combination of SHP and PTX can enhance the anti-tumor efficacy of PTX and mitigate its pro-metastatic effects in a 4T1 breast cancer mouse model.
    Methods: Female Balb/c mice were injected with 4T1 breast cancer cells and then divided into four treatment groups: control, PTX, SHP, and PTX+SHP. The combination of SHP and PTX was evaluated using bioluminescence imaging (BLI), histological analysis, and hematoxylin and eosin (HE) staining to assess lung metastasis. Flow cytometry was employed to analyze immune cell populations, including tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), and cytotoxic T cells (CD8+ and CD4+).
    Results: SHP alone did not significantly inhibit lung metastasis but the combination of PTX and SHP led to a marked reduction in lung lesions, as confirmed by BLI and histological analysis. SHP improved the overall health of PTX-treated mice, reducing their body weight loss and mortality. Flow cytometry revealed that the combination therapy reduced the infiltration of M2 macrophages, MDSCs, and Tregs, while increasing the proportion of antitumor M1 macrophages, cytotoxic CD8+ T cells, and helper CD4+ T cells.
    Conclusions: The combination of PTX and SHP has a synergistic effect, reducing lung metastasis and modulating immune cell populations within the TME. These results suggest that integrating traditional Chinese medicine with standard chemotherapy can enhance therapeutic efficacy and reduce adverse effects.
    Keywords:  Paclitaxel; Shenhuang plaster; breast cancer; lung metastasis; tumor microenvironment
    DOI:  https://doi.org/10.3389/fonc.2025.1531493
  20. World J Gastroenterol. 2025 Mar 14. 31(10): 103454
    Advances in imaging techniques for tumor microenvironment evaluation in hepatocellular carcinoma.
    Li-Li Wang, Fa-Chang Zhang, Han-Xin Xu, Dian-Dian Deng, Bing-Jie Ren, Qi Tan, Ya-Xin Liu, Wen-Hui Zhao, Jia-Le Lu.
      The tumor microenvironment (TME) plays a critical role in the development and treatment of liver cancer, which ranks sixth in incidence and third in mortality worldwide, according to the "Global Cancer Statistics 2022". Hepatocellular carcinoma (HCC), the most common form of liver cancer, is heavily influenced by the TME, which affects tumor growth, invasion, metastasis, and the response to various treatments. Despite advancements in surgery, liver transplantation, targeted therapies, and immunotherapy, the complexity of the TME often limits treatment efficacy, especially in advanced-stage HCC cases. The TME consists of a dynamic interaction between tumor cells, immune cells, fibroblasts, blood vessels, and signaling molecules, all of which contribute to cancer progression and therapy resistance. Assessing the HCC TME is essential for designing effective, personalized treatments and improving patient outcomes. Recent research highlights the value of imaging technologies as non-invasive tools to evaluate the TME, offering new possibilities for more targeted therapies and better prognosis monitoring in HCC patients.
    Keywords:  Hepatocellular carcinoma; Imaging diagnosis; Molecular imaging; Non-invasive assessment; Tumor microenvironment
    DOI:  https://doi.org/10.3748/wjg.v31.i10.103454
  21. J Transl Med. 2025 Mar 17. 23(1): 341
    New insights on anti-tumor immunity of CD8+ T cells: cancer stem cells, tumor immune microenvironment and immunotherapy.
    Yibin Lin, Yifu Song, Yaochuan Zhang, Xiaodong Li, Liang Kan, Sheng Han.
      Recent breakthroughs in tumor immunotherapy have confirmed the capacity of the immune system to fight several cancers. The effective means of treating cancer involves accelerating the death of tumor cells and improving patient immunity. Dynamic changes in the tumor immune microenvironment alter the actual effects of anti-tumor drug production and may trigger favorable or unfavorable immune responses by modulating tumor-infiltrating lymphocytes. Notably, CD8+ T cells are one of the primary tumor-infiltrating immune cells that provide anti-tumor response. Tumor cells and tumor stem cells will resist or evade destruction through various mechanisms as CD8+ T cells exert their anti-tumor function. This paper reviews the research on the regulation of tumor development and prognosis by cancer stem cells that directly or indirectly alter the role of tumor-infiltrating CD8+ T cells. We also discuss related immunotherapy strategies.
    Keywords:  Cancer prognosis; Cancer stem cell (CSC); Cytotoxic CD8+ T lymphocyte (CTL); Immunotherapy; Tumor immune microenvironment (TIME)
    DOI:  https://doi.org/10.1186/s12967-025-06291-y
  22. Front Oncol. 2025 ;15 1530541
    Adoptive cell therapy against tumor immune evasion: mechanisms, innovations, and future directions.
    Liqin Ruan, Lu Wang.
      Tumors employ a range of strategies to evade detection and eradication by the host's immune system. These include downregulating antigen expression, altering antigen presentation processes, and inhibiting immune checkpoint pathways. etc. Adoptive Cell Therapy (ACT) represents a strategy that boosts anti-tumor immunity. This is achieved by amplifying or genetically engineering immune cells, which are either sourced from the patient or a donor, in a laboratory setting. Subsequently, these cells are reintroduced into the patient to bolster their immune response against cancer. ACT has successfully restored anti-tumor immune responses by amplifying the activity of T cells from patients or donors. This review focuses on the mechanisms underlying tumor escape, including alterations in tumor cell antigens, the immunosuppressive tumor microenvironment (TME), and modulation of immune checkpoint pathways. It further explores how ACT can avddress these factors to enhance therapeutic efficacy. Additionally, the review discusses the application of gene-editing technologies (such as CRISPR) in ACT, highlighting their potential to strengthen the anti-tumor capabilities of T cells. Looking forward, the personalized design of ACT, combined with immune checkpoint inhibitors and targeted therapies, is expected to significantly improve treatment outcomes, positioning this approach as a key strategy in the field of cancer immunotherapy.
    Keywords:  adoptive cell therapy; cancer mechanisms; immune evasion; personalized treatment; tumor microenvironment
    DOI:  https://doi.org/10.3389/fonc.2025.1530541
  23. Mol Ther Oncol. 2024 Dec 19. 32(4): 200869
    Senescence-associated secretory phenotype regulation by dual-drug delivery biomimetic nanoplatform for enhanced tumor chemotherapy.
    Ajay Prakash, Travis Gates, Emil Lou.
      Wang and colleagues provide a comprehensive evaluation of a biomimetic platform in which a specially designed drug delivery system, referred to in the manuscript as mPtP@Lipo, is used to increased penetration of dense stromatous tumors. This work represents a significant advancement in the treatment of desmoplastic tumors by targeting the tumor microenvironment (TME), particularly focusing on remodeling cancer-associated fibroblasts (CAFs). The study leverages previous work, which has demonstrated that platinum (Pt)-based chemotherapeutic regimens can induce a senescence-associated secretory phenotype (SASP) through persistent DNA damage, which can contribute to an immunosuppressive tumor immune microenvironment.
    DOI:  https://doi.org/10.1016/j.omton.2024.200869
  24. Trends Cancer. 2025 Mar 19. pii: S2405-8033(25)00055-X. [Epub ahead of print]
    Targeting novel immune checkpoints in the B7-H family: advancing cancer immunotherapy from bench to bedside.
    Yiming Luo, Ye Yuan, Dan Liu, Haoxin Peng, Lin Shen, Yang Chen.
      The B7-H family of immune checkpoint molecules is a crucial component of the immune regulatory network for tumors, offering new opportunities to modulate the tumor microenvironment (TME). The B7-H family - which includes B7-H2 (inducible T cell costimulatory ligand, ICOSL), B7-H3, B7-H4, B7-H5 (V-domain immunoglobulin suppressor of T cell activation, VISTA), B7-H6, and B7-H7 (HHLA2) - is known for its diverse roles in regulating innate and adaptive immunity. These molecules can exhibit co-stimulatory or co-inhibitory effects on T cells, influencing processes such as T cell activation, differentiation, and effector functions, and they are involved in the recruitment and polarization of various immune cells. This review explores the structural characteristics, receptor-ligand interactions, and signaling pathways associated with each B7-H family member. We also discuss the family's impact on tumor immunity and potential therapeutic strategies.
    Keywords:  B7-H family; cancer immunotherapy; immune checkpoints; tumor microenvironment
    DOI:  https://doi.org/10.1016/j.trecan.2025.02.007
  25. BMC Cancer. 2025 Mar 14. 25(1): 474
    Impacts of combining PD-L1 inhibitor and radiotherapy on the tumour immune microenvironment in a mouse model of esophageal squamous cell carcinoma.
    Zihao Yin, Hongfang Zhang, Ke Zhang, Jing Yue, Rongjun Tang, Yaping Wang, Qinghua Deng, Qingqing Yu.
       BACKGROUND: The combination of radiation with immune checkpoint inhibitors (ICIs) has been demonstrated to display synergistic effects in solid cancers. Nevertheless, the anti-tumor effect of combining radiation with programmed cell death 1 ligand 1 (PD-L1) inhibitor in esophageal squamous cell carcinoma (ESCC) has remained unclear. Therefore, the objectives of our study were to evaluate the anti-tumor effects of PD-L1 inhibitors combined with radiotherapy in a mouse model of ESCC and to depict the immune landscape within the tumor microenvironment (TME).
    METHODS: Murine ESCC cells (mEC25) were injected subcutaneously into the right flanks of C57BL/6 mice. Tumor-bearing mice were exposed to different treatments: IgG antibody (control), anti-PD-L1 antibody, radiation, or radiation + anti-PD-L1 antibody. Tumor growth and survival time of mice were monitored. Tumour immune microenvironment was assessed by flow cytometry, including CD4+T cells, CD8+T cells, regulatory T cells (Tregs), tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), and the activation and exhaustion of CD8+T cell. In addition, transcriptomic analysis was used to examine the changes in immune gene expression in the TME.
    RESULTS: Radiotherapy combined with anti-PD-L1 inhibitors (radioimmunotherapy) synergistically enhanced anti-tumor immune response, leading to decreased tumor growth and prolonged survival of tumor-bearing mice. The radioimmunotherapy increased the infiltration of CD8+ T cells, the ratio of CD8+ T cells to Tregs, the population of central memory CD8+ T cells (TCM), interferon-gamma (IFN-γ) secretion of tumor-infiltrating CD8+ T cells, and reduced the accumulation of M2-type TAMs and Tregs in the TME in mouse model. In addition, the radioimmunotherapy induced anti-tumor immune response in the spleen and tumor-draining lymph node (TDLN). Moreover, transcriptomic analysis suggested that the radioimmunotherapy promoted the activation of immune regulatory pathways and increased the expression of cytokines such as CXCL9 and CXCL10, thus creating an immunoinflammatory tumor microenvironment.
    CONCLUSIONS: Our research revealed that anti-PD-L1 inhibitors combined with radiotherapy caused systemic anti-tumor immunity by reshaping the immune microenvironment in a mouse model of ESCC.
    Keywords:  Esophageal squamous cell carcinoma; Programmed death ligand 1; Radiotherapy; Tumor microenvironment
    DOI:  https://doi.org/10.1186/s12885-025-13801-0
  26. Int J Pharm. 2025 Mar 16. pii: S0378-5173(25)00319-9. [Epub ahead of print] 125483
    CD44-Targeted nanoparticles for remodeling the tumor microenvironment in a 3D Macrophage-Embedded ovarian cancer model with stem Cell-Like features.
    Samjhana Shrestha, Anil Giri, Prabhat Shrestha, Seho Kweon, In-Sun Hong, Jong Ho Park, Jong-Sun Kang, Jee-Heon Jeong, Ha Rin Kim, Simmyung Yook.
      Ovarian cancer frequently develops resistance to chemotherapy, which is driven by cancer stem cells (CSCs) and an immunosuppressive tumor microenvironment (TME) shaped by tumor-associated macrophages (TAMs). This study explored the therapeutic potential of CD44-targeted, docetaxel (DTX)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (CD44-PLGA-DTX NPs) in overcoming chemoresistance in ovarian cancer. A 3D spheroidal model incorporating SKOV3 ovarian cancer cells and TAMs was developed to mimic the TME for in vitro investigations. CD44-PLGA-DTX NPs exhibited significantly enhanced cellular uptake within the macrophage-embedded SKOV3 spheroids, which resulted in reduced cell viability and a reversal of chemoresistance. Cytokine profiling further revealed that the NPs promoted TAM polarization from the protumor M2 phenotype to the antitumor M1 phenotype, thus fostering an antitumor immune environment. These findings highlight the potential of CD44-targeted NPs as a dual-targeted therapeutic strategy, targeting both CSCs-driven tumor growth and TME reprogramming, thereby improving ovarian cancer treatment outcomes.
    Keywords:  3D spheroid; CD44-antibody; Nanoparticles; Ovarian cancer stem cells; PLGA
    DOI:  https://doi.org/10.1016/j.ijpharm.2025.125483
  27. Mol Cancer Ther. 2025 Mar 19.
    CD24-targeted CAR-T cells mediated long-term anti-tumor efficacy through activation of endogenous tumor immune responses.
    Yong Huang, Xiao Yang, Jing Li, Weilin Zhou, Fengling Wang, Jiaqian Li, Yalan Zhang, Feiyang Yan, Haozhan Gao, Xinyu Gu, Sha Luo, Yuening Yang, Mei Liu, Xiao Liang, Lin Jiang, Maorong Fu, Jinhua Su, Yuquan Wei, Wei Wang.
      Chimeric antigen receptor T cell (CAR-T) therapy has achieved remarkable progress in the treatment of B-cell malignancies, while suboptimal therapeutic outcomes have been observed in solid tumors. Immunosuppression from microenvironment of tumors causing decreased killing ability, poor expansion and persistence of CAR-T cells results in reduced efficacy. Endeavors aimed at eliciting endogenous immune responses have been found to enhance and sustain the anti-tumor effects of CAR-T therapy. Here we reported that CAR-T cells targeting CD24, a potential tumor biomarker and an innate immune checkpoint molecular, evoked robust anti-tumor efficacy and elicited long-term tumor regression. CD24-targeted CAR-T (CD24 CAR-T) cells showed strong cytotoxicity to CD24-positive cancer cells in vitro and mediated inhibition of tumor growth in immunodeficient mice. Moreover, in immunocompetent mice, CD24 CAR-T cells exhibited robust anti-tumor ability without side effects. Of note, mice received CD24 CAR-T cells withstand both CD24-positive and negative tumors rechallenge. It is detected that high level of IFN-γ release in splenic lymphocytes of the rechallenged mice, as well as tumor-reactive antibody in serum, indicating the endogenous tumor immune responses was activated. In summary, our findings showed that CD24 CAR-T cells targeting immune checkpoint have superior antitumor efficacy in preclinical models and may provide a strategy for the treatment of solid tumors.
    DOI:  https://doi.org/10.1158/1535-7163.MCT-24-0597
  28. Front Immunol. 2025 ;16 1538635
    Neutrophils in colorectal cancer: mechanisms, prognostic value, and therapeutic implications.
    Xingyue Wang, Shukang He, Xiangmei Gong, Shijun Lei, Qianwen Zhang, Junqi Xiong, Yang Liu.
      Neutrophils, the most abundant myeloid cells in human peripheral blood, serve as the first defense line against infection and are also significantly involved in the initiation and progression of cancer. In colorectal cancer (CRC), neutrophils exhibit a dual function by promoting tumor events and exerting antitumor activity, which is related to the heterogeneity of neutrophils. The neutrophil extracellular traps (NETs), gut microbiota, and various cells within the tumor microenvironment (TME) are involved in shaping the heterogeneous function of neutrophils. This article provides an updated overview of the complex functions and underlying mechanisms of neutrophils in CRC and their pivotal role in guiding prognosis assessment and therapeutic strategies, aiming to offer novel insights into neutrophil-associated treatment approaches for CRC.
    Keywords:  colorectal cancer; gut microbiota; neutrophils; prognosis; therapies; tumor microenvironment
    DOI:  https://doi.org/10.3389/fimmu.2025.1538635
  29. Exp Cell Res. 2025 Mar 19. pii: S0014-4827(25)00127-2. [Epub ahead of print] 114531
    SNHG family lncRNAs: key players in the breast cancer progression and immune cell's modulation.
    Mohamed J Saadh, Junainah Abd Hamid, Malathi H, Syeda Wajida Kazmi, Thabit Moath Omar, Ashish Sharma, M Ravi Kumar, Tushar Aggarwal, Fadhil Feez Sead.
      Breast cancer, a highly prevalent form of cancer worldwide, has observed a steady increase in its prevalence over the past few decades. This rise can be attributed to the complex nature of the disease, characterized by its heterogeneity, ability to metastasize, and resistance to various treatment. In the field of cancer research, long non-coding RNAs (lncRNAs) are of special interest, which play an important role in the development and progression of various tumors, including breast cancer. LncRNAs affect the tumor microenvironment by attracting diverse immunosuppressive factors and controlling the differentiation of immune cells, often referred to as myeloid and lymphoid cells, which contributes to immune escape of tumor cells. Among the lncRNA families, the small nucleolar RNA host gene (SNHG) family has been found to be dysregulated in breast cancer. These SNHGs have been implicated in crucial cellular processes such as cell proliferation, invasion, migration, resistance to therapies, apoptosis, as well as immune cell regulation and differentiation. Consequently, they have great potential as diagnostic and prognostic biomarkers as well as potential therapeutic targets for breast cancer. In this comprehensive review, we aim to summarize the recent advances in the study of SNHGs in breast cancer pathogenesis and their role in regulating the activity of immune cells in the tumor microenvironment through affecting SNHGs/miRNA/mRNA pathways, with the aim of providing new insights into the treatment of breast cancer.
    Keywords:  Breast cancer; Immune cells; Metastasis; SNHGs family; Therapy resistance; lncRNA
    DOI:  https://doi.org/10.1016/j.yexcr.2025.114531
  30. Mol Cancer. 2025 Mar 19. 24(1): 86
    Extracellular vesicles in cancer´s communication: messages we can read and how to answer.
    Alena Semeradtova, Michaela Liegertova, Regina Herma, Magdalena Capkova, Chiara Brignole, Genny Del Zotto.
      Extracellular vesicles (EVs) are emerging as critical mediators of intercellular communication in the tumor microenvironment (TME), profoundly influencing cancer progression. These nano-sized vesicles, released by both tumor and stromal cells, carry a diverse cargo of proteins, nucleic acids, and lipids, reflecting the dynamic cellular landscape and mediating intricate interactions between cells. This review provides a comprehensive overview of the biogenesis, composition, and functional roles of EVs in cancer, highlighting their significance in both basic research and clinical applications. We discuss how cancer cells manipulate EV biogenesis pathways to produce vesicles enriched with pro-tumorigenic molecules, explore the specific contributions of EVs to key hallmarks of cancer, such as angiogenesis, metastasis, and immune evasion, emphasizing their role in shaping TME and driving therapeutic resistance. Concurrently, we submit recent knowledge on how the cargo of EVs can serve as a valuable source of biomarkers for minimally invasive liquid biopsies, and its therapeutic potential, particularly as targeted drug delivery vehicles and immunomodulatory agents, showcasing their promise for enhancing the efficacy and safety of cancer treatments. By deciphering the intricate messages carried by EVs, we can gain a deeper understanding of cancer biology and develop more effective strategies for early detection, targeted therapy, and immunotherapy, paving the way for a new era of personalized and precise cancer medicine with the potential to significantly improve patient outcomes.
    Keywords:  Biomarkers; Cancer; Extracellular vesicles; Immune evasion; Liquid biopsy; Metastasis; Targeted therapy; Tumor microenvironment
    DOI:  https://doi.org/10.1186/s12943-025-02282-1
  31. Sci Adv. 2025 Mar 21. 11(12): eadt2117
    CD38-mediated metabolic reprogramming promotes the stability and suppressive function of regulatory T cells in tumor.
    Ishita Sarkar, Debashree Basak, Puspendu Ghosh, Anupam Gautam, Arpita Bhoumik, Praveen Singh, Anwesha Kar, Shaun Mahanti, Snehanshu Chowdhury, Lagnajita Chakraborty, Soumya Mondal, Ramanuj Mukherjee, Shikhar Mehrotra, Saikat Majumder, Shantanu Sengupta, Sandip Paul, Shilpak Chatterjee.
      In the tumor microenvironment (TME), regulatory T cells (Tregs) adapt their metabolism to thrive in low-glucose, high-lactate conditions, but the mechanisms remain unclear. Our study identifies CD38 as a key regulator of this adaptation by depleting nicotinamide adenine dinucleotide (oxidized form) (NAD+), redirecting lactate-derived pyruvate toward phosphoenolpyruvate and bypassing the tricarboxylic acid (TCA) cycle. This prevents accumulation of α-ketoglutarate, which destabilizes Tregs by inducing hypermethylation at the Foxp3 locus. Restoring NAD+ with nicotinamide mononucleotide reverses this adaptation, pushing Tregs back to the TCA cycle and reducing their suppressive function. In YUMM1.7 melanoma-bearing mice, small-molecule CD38 inhibition selectively destabilizes intratumoral Tregs, sparking robust antitumor immunity. These findings reveal that targeting the CD38-NAD+ axis disrupts Tregs metabolic adaptation and offers a strategy to enhance antitumor responses.
    DOI:  https://doi.org/10.1126/sciadv.adt2117
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