bims-flamet Biomed News
on Cytokines and immunometabolism in metastasis
Issue of 2025–10–05
twenty papers selected by
Peio Azcoaga, Biodonostia HRI
  1. Immunology, immunotherapy, and the tumor microenvironment in hepatocellular carcinoma: a comprehensive review.
  2. The Tumor Microenvironment: Impact on Tumor Growth, Metastasis, and Therapeutic Resistance: A Systematic Review.
  3. Immunotherapy strategies targeting tumor-associated macrophages and their mechanisms of action in tumor progression.
  4. Exploring the tumor microenvironment in solid cancer: From biology to therapy.
  5. [Myeloid tumors and antitumor innate immunity].
  6. The multifaceted role of YAP in the tumor microenvironment and its therapeutic implications in cancer.
  7. Current strategies for armoring chimeric antigen receptor T-cells to overcome barriers of the solid tumor microenvironment.
  8. Improving Immune Checkpoint Therapy in the Tumor Microenvironment by Targeting T Cell Metabolism.
  9. CAF-derived exosomes: orchestrators of dysregulated signaling pathways in breast cancer progression.
  10. Tumor Microenvironment Metabolism-Modulating Nanomedicines for Enhancing Anti-Tumor Immunity.
  11. Glutamine metabolism and ammonia death: targeted modulation for enhanced cancer immunotherapy.
  12. Tumor-infiltrating lymphocytes and tumor-associated macrophages in cancer immunoediting: a targetable therapeutic axis.
  13. Recent advances in the investigation of the regulatory network underlying reactive nitrogen species-mediated tumorigenesis: molecular mechanisms and targeted therapeutic strategies.
  14. Neutrophils and cancer immunotherapy: Potential mechanisms and challenges in breast cancer - a narrative review.
  15. Matter of Fat: Cancer-Associated Adipocytes as Mediators of Tumor Progression and Immune Evasion.
  16. Bridging the gap: ferroptosis of immune cells in the tumor microenvironment.
  17. Multifunctional exosome-driven tumor immunotherapy sensitization: converting intratumoral bacteria into antitumor fighters.
  18. pH-Triggered Cell Surface Anti-Hapten Antibody Recruitment by Amphiphilic Block Copolymers Containing Ionizable Amines and Haptens in the Hydrophobic Block.
  19. The mechanical landscape of cancer: Exploring mechanical characteristics-based therapeutic approaches.
  20. In Vitro Model for Studying Interaction of Immune Cells and Cancer Cells.
  1. Expert Rev Clin Immunol. 2025 Sep 29.
    Immunology, immunotherapy, and the tumor microenvironment in hepatocellular carcinoma: a comprehensive review.
    Miho Akabane, Yuki Imaoka, Ghee Rye Lee, Timothy M Pawlik.
       INTRODUCTION: Hepatocellular carcinoma (HCC) is a major cause of cancer-related death globally, characterized by an immunosuppressive tumor microenvironment (TME) that impairs immune surveillance. Immunotherapy has emerged as a transformative option; however, durable responses remain limited. The purpose of this review is to synthesize recent advances in HCC immunology, immunotherapy, and the TME.
    AREAS COVERED: Literature was identified via PubMed and ClinicalTrials.gov (January 2001-May 2025), focusing on clinical and translational studies. We outline the immunological landscape of HCC, emphasizing the roles of T cells, natural killer cells, macrophages, dendritic cells, myeloid-derived suppressor cells, and regulatory T cells in shaping tumor immunity. TME components include cancer-associated fibroblasts, tumor-associated macrophages, suppressive cytokines, angiogenesis, hypoxia, metabolic reprogramming, and the gut-liver axis. We examine their interactions with immunotherapy, mechanisms of resistance, and combination strategies. Emerging biomarkers - such as tertiary lymphoid structures, PD-L1, tumor mutational burden, gene signatures, and gut microbiota - are reviewed for patient stratification.
    EXPERT OPINION: Immunotherapy has reshaped HCC management, but resistance, biomarker limitations, and heterogeneity remain major challenges. Advances will require TME reprogramming, multi-parametric biomarkers, and personalized strategies. Integration with targeted and locoregional approaches may achieve durable responses and move toward precision immuno-oncology, transforming HCC into a manageable or curable disease.
    Keywords:  Hepatocellular Carcinoma; Immunology; Immunotherapy; Review; Tumor Microenvironment
    DOI:  https://doi.org/10.1080/1744666X.2025.2568904
  2. Curr Mol Med. 2025 Sep 26.
    The Tumor Microenvironment: Impact on Tumor Growth, Metastasis, and Therapeutic Resistance: A Systematic Review.
    Jiazhi Yan, Shuo Tu.
       INTRODUCTION: This systematic review assesses the role of the tumor microenvironment (TME) in cancer progression and therapy resistance by defining drug-microenvironment interactions and determining the molecular determinants in the TME that could help improve the efficacy of administered treatments and alleviate existing adverse effects.
    METHODS: This systematic review follows the PRISMA protocol and the PICOS selection framework to retrieve studies from PubMed/MEDLINE, Web of Science, Scopus, and the Cochrane Library. Only original human-related research published in English between 2008 and 2023 was used to explore the reciprocal relation between tumor cells and TME components. The ROBINS-I tool assessed the risk of bias.
    RESULTS: Out of 258 articles initially identified, 15 met the inclusion criteria for this review. The results showed that TMEs significantly influence treatment outcomes in cancer progression, metastasis, and drug resistance. Focusing on TMEs like CAFs, immune cells, and ECM enhances drug efficacy. The study highlighted potential strategies to improve drug delivery, suppress metastatic processes, and restore immune function, ultimately leading to better outcomes for cancer patients.
    DISCUSSION: Original evidence suggests that Cancer-Associated Fibroblasts (CAFs), immune cells, and Extracellular Matrix (ECM) contribute to therapeutic resistance and metastasis within the TME. They also promote metastasis by inducing Epithelial- Mesenchymal Transition (EMT) and affecting Cancer Stem Cell (CSC) populations. Moreover, the immunosuppressive TME consists of regulatory T cells and myeloidderived suppressor cells that allow tumors to evade the immune system, a concern for immunotherapy.
    CONCLUSION: The TME plays a vital role in cancer development, metastasis formation, and therapy failure. The perspectives for innovative ECM-modulating treatments and interventions targeting the direct interactions between TME and cancer cells can be revolutionary and suggest better outcomes for treatment-naïve and refractory cancers. Future research should use these results as inputs to apply clinical and therapy studies to enhance cancer management outcomes.
    Keywords:  Cancer-associated Fibroblasts (CAFs); Extracellular Matrix (ECM).; Immune Evasion; Metastasis; Therapeutic Resistance; Tumor Microenvironment (TME)
    DOI:  https://doi.org/10.2174/0115665240388282250903221303
  3. Front Immunol. 2025 ;16 1680455
    Immunotherapy strategies targeting tumor-associated macrophages and their mechanisms of action in tumor progression.
    Haixia Zhu, Jingjing Shao, Lili Shao, Liuhuan Cai, Chunyan Gu, Qin Ge, Jibin Liu.
      The tumor microenvironment significantly influences the aggressive invasive characteristics of human solid tumors, with the infiltration of immune cells being a defining feature of tumor advancement. Among the diverse cell types present in the tumor microenvironment, tumor-associated macrophages (TAMs) stand out as crucial regulatory centers in the interplay between tumors and the immune system. Recent developments in single-cell sequencing technologies, combined with an expanding body of research, have revealed the functional diversity and heterogeneity of TAMs, as well as the mechanisms through which they interact within the tumor microenvironment. This indicates that TAMs could represent innovative targets for therapies aimed at tumors, thus promoting the creation of tailored anti-cancer strategies. This article provides a review of the various types of TAMs, their influence on tumor development and progression, their regulatory functions in tumor activities, and the progress in tumor immunotherapy that focuses on targeting TAMs.
    Keywords:  immune cell; tumor immunotherapy; tumor microenvironment; tumor treatment; tumor-associated macrophages
    DOI:  https://doi.org/10.3389/fimmu.2025.1680455
  4. Methods Cell Biol. 2025 ;pii: S0091-679X(25)00078-0. [Epub ahead of print]198 359-385
    Exploring the tumor microenvironment in solid cancer: From biology to therapy.
    Zubair Ahmed, Muneeb Ullah, Danish Zeshan, Shahid Ullah Khan, Fawad Ali, Abdul Wahab.
      Cancer is a major global health concern marked by uncontrolled cellular proliferation and genetic modifications leading to malignancy. The disease's complexity encompasses various forms of cancer, increased rates of diagnosis and prognosis and numerous treatment modalities, including surgery, chemotherapy, and radiation, each confronting problems such as medication resistance and side effects. Solid tumors, comprising approximately 85 % of malignancies, provide significant treatment challenges due to their uneven vascular supply and interstitial pressure, resulting in inadequate medication distribution and therapeutic failure. The tumor microenvironment (TME) comprises cancer cells and diverse supportive cells such as immune cells, endothelial cells and fibroblasts, which interact to facilitate tumor growth and progression. T lymphocytes, B lymphocytes, natural killer cells, and macrophages are only a few types of immune cells that can aid or impede cancer progression, which makes treatment more complicated. In this chapter we will explore the TME in solid cancers, focusing on its role in cancer biology and therapeutics strategies. In the future, advancing therapies that more precisely target TME components will minimize treatment resistance and improve patient outcomes.
    Keywords:  Chemotherapy; Immune cells; Solid tumors; Tumor microenvironment
    DOI:  https://doi.org/10.1016/bs.mcb.2025.02.020
  5. Rinsho Ketsueki. 2025 ;66(9): 883-890
    [Myeloid tumors and antitumor innate immunity].
    Susumu Goyama.
      The success of immune checkpoint inhibitors and CAR-T cell therapies has established immunotherapy as the "fourth pillar" of cancer treatment, alongside surgery, radiation, and chemotherapy. However, the therapeutic efficacy of immunotherapy for myeloid malignancies remains limited. While tumor immunology research has traditionally focused on T cells, attention has recently shifted to the roles of innate immune cells in the tumor microenvironment. These cells, which include macrophages, myeloid-derived suppressor cells, dendritic cells, and natural killer cells, have been found to play significant roles in the development and progression of myeloid malignancies. To develop effective immunotherapies for myeloid malignancies, it is essential to deepen our understanding of the roles of innate immunity within the bone marrow microenvironment and explore strategies to harness these mechanisms. This paper reviews the latest findings on innate immunity in myeloid malignancies and discusses the potential of immunotherapies that leverage innate immune responses.
    Keywords:  Innate immunity; Myeloid tumors; NK cells; SETDB1
    DOI:  https://doi.org/10.11406/rinketsu.66.883
  6. Exp Mol Med. 2025 Oct 01.
    The multifaceted role of YAP in the tumor microenvironment and its therapeutic implications in cancer.
    Hyung-Sik Kim, Jeong-Seok Nam.
      The tumor microenvironment (TME) plays a critical role in cancer progression, immune evasion and therapeutic resistance. The transcriptional coactivators YAP and TAZ, key effectors of the Hippo signaling pathway, have emerged as central regulators of TME remodeling. YAP/TAZ are activated in both tumor and stromal compartments, where they function as mechanotransducers and integrate canonical Hippo pathway suppression, noncanonical microenvironmental cues and genetic or epigenetic signals to drive transcriptional programs. These changes collectively facilitate tumor immune evasion. YAP/TAZ further promote angiogenesis and upregulate PD-L1 expression in tumor cells and cancer-associated fibroblasts, and a subset of immunosuppressive cells in the TME, contributing to resistance to ICB. In addition to their tumor-intrinsic and stromal functions, YAP/TAZ impair antitumor immunity by altering immune cell differentiation and dampening effector responses. Targeting the YAP/TAZ-TEAD axis has shown potential efficacy when combined with immune checkpoint inhibitors, chimeric antigen receptor T cell therapies and tumor vaccines. Although challenges such as tumor selectivity and resistance mechanisms persist, advances in single-cell and spatial transcriptomics are enabling the dissection of YAP/TAZ-regulated networks and guiding the development of more precise therapeutic strategies. Collectively, YAP/TAZ inhibition offers a promising avenue to reprogram the TME and enhance the efficacy of next-generation cancer immunotherapies.
    DOI:  https://doi.org/10.1038/s12276-025-01551-9
  7. Front Immunol. 2025 ;16 1643941
    Current strategies for armoring chimeric antigen receptor T-cells to overcome barriers of the solid tumor microenvironment.
    Dorothy D Yang, William Macmorland, James N Arnold.
      Chimeric antigen receptor (CAR) T-cell therapy is a transformative immunotherapeutic approach, yet its application in solid tumors is hindered by the immunosuppressive tumor microenvironment (TME). The TME restricts T-cell trafficking, impairs effector functions, and promotes exhaustion through soluble factors, metabolic stress, and suppressive cell populations. Recent efforts to enhance CAR T-cell efficacy have focused on armoring strategies that 'reprogram' and 'boost' T-cell responses within the TME. These include engineered expression of dominant-negative receptors or cytokine-releasing constructs (such as IL-12 and IL-18) to reshape the local immune milieu and improve T-cell effector function, synthetic Notch receptors for inducible gene expression, and chemokine receptor knock-ins to improve tumor infiltration. Additional approaches aim to modulate intrinsic metabolic pathways to improve CAR T-cell persistence under hypoxic or nutrient-deprived conditions. Armoring strategies that recruit bystander or endogenous immune cells also activate broader anti-tumor immunity that prevents antigen escape and may induce more durable anti-tumor responses. This review highlights the molecular and cellular mechanisms by which current armoring strategies enhance CAR T-cell functions in solid tumors, offering a perspective on improving immune cell engineering for overcoming the hurdles encountered in deploying these therapies against solid cancers.
    Keywords:  T-cells; armored; chimeric antigen receptor; immunosuppression; immunotherapy; microenvironment; solid tumors; stroma
    DOI:  https://doi.org/10.3389/fimmu.2025.1643941
  8. Endocr Metab Immune Disord Drug Targets. 2025 Sep 02.
    Improving Immune Checkpoint Therapy in the Tumor Microenvironment by Targeting T Cell Metabolism.
    Jun Wei, Baozhen An, Renchao Dong, Xinyi Tu, Yifei Dong, Yuang Liu, Yanqiu Liu.
      To meet the increased nutrient requirements associated with rapid cellular proliferation, tumor cells undergo metabolic reprogramming, characterized by a substantial increase in the production of energy and precursor molecules necessary for biosynthetic processes. Similarly, T cells experience metabolic reprogramming to support their proliferation and immunological functions, leading to metabolic competition with tumor cells within the tumor microenvironment (TME). This metabolic competition adversely affects T cell activation, proliferation, and immune function, primarily due to the limited availability of glucose, lipids, and amino acids. Furthermore, cytokines and immune checkpoints significantly impact T cell-mediated immunoreactivity. Modulating the metabolism of tumor cells and T cell-mediated immune evasion within the TME is of paramount importance. Notably, the metabolism of small-molecule target agents has garnered considerable attention in the context of the TME. This study aimed to examine the influence of various microenvironmental factors on T cell metabolism and explore corresponding innovative therapeutic approaches, thereby offering a comprehensive array of potential clinical strategies for cancer prevention and treatment.
    Keywords:  T cell metabolism; combination therapy.; immune checkpoint; nutrient competition; tumor immunotherapy; tumor microenvironment
    DOI:  https://doi.org/10.2174/0118715303400871250821103310
  9. Naunyn Schmiedebergs Arch Pharmacol. 2025 Sep 27.
    CAF-derived exosomes: orchestrators of dysregulated signaling pathways in breast cancer progression.
    Almuthana K Hameed, Safia Obaidur Rab, Thanaa Amir Ahmed, Muktesh Chandra, Jaafaru Sani Mohammed, Renukajyothi S, Priya Priyadarshini Nayak, Prakhar Tomar, Ahmed Hussn, Abbas Fadhel Ali.
      Cancer-associated fibroblasts (CAFs) play a pivotal role in breast cancer (BC) progression by modulating the tumor microenvironment through exosome-mediated interactions. CAF-derived exosomes are rich in bioactive molecules such as metabolites, proteins, and non-coding RNAs that influence metabolic reprogramming in BC cells. These exosomes facilitate the transfer of metabolic enzymes and signaling molecules that enhance glycolysis, lipid metabolism, and oxidative phosphorylation, thereby supporting tumor growth, therapy resistance, and metastasis. This review highlights the molecular mechanisms underlying the role of CAF-derived exosomes in BC metabolism, with a focus on their contributions to metabolic plasticity and tumor progression. Potential therapeutic strategies targeting CAF exosome biogenesis, release, or uptake will also be discussed to shed light on innovative approaches for disrupting this metabolic symbiosis.
    Keywords:  Breast cancer; Cancer-associated fibroblasts; Exosomes; Tumor microenvironment
    DOI:  https://doi.org/10.1007/s00210-025-04635-5
  10. Small. 2025 Oct 03. e09685
    Tumor Microenvironment Metabolism-Modulating Nanomedicines for Enhancing Anti-Tumor Immunity.
    Jiajie Chen, Simiao Fei, Zhihao Cao, Xinchun Liu, Weizhi Ji, Hangrong Chen, Yuyu Niu, Zebin Yang.
      Metabolic reprogramming within the tumor microenvironment (TME) sustains tumor cell survival, suppresses immune cell functionality, and drives immunosuppression, thereby impairing immunotherapeutic effectiveness and exacerbates clinical challenges. Encouragingly, advances in nanomedicine offer promising strategies to precisely and effectively remodel TME metabolism, including glycolysis, amino acid metabolism, lipid metabolism, etc., to potentiate anti-tumor immunity. This review delineates distinctive metabolic pathways in tumor cells, immune cells, and cancer stem cells (CSCs) within the immunosuppressive niches, detailing the rational design of nanomedicines with TME metabolism-modulating capabilities to enhance cancer immunotherapy while elucidating the concrete action mechanisms between nano-enabled metabolic modulation and immune response activation. Despite the promise, the pivotal challenges listed at the end demand resolution to advance TME metabolism-modulating nanotherapeutics for meeting personalized clinical anti-tumor demands.
    Keywords:  cancer immunotherapy; immunosuppression; metabolic modulation; nanomedicine; tumor microenvironment
    DOI:  https://doi.org/10.1002/smll.202509685
  11. Front Immunol. 2025 ;16 1643017
    Glutamine metabolism and ammonia death: targeted modulation for enhanced cancer immunotherapy.
    Fei Du, Linlin Xiao, Wang Guojun, Qian Dai, Junxin Li, Xin Zhao, Qimin Zhang, Lan Yang, Yujie Liu, Yidan Hu, Bo Wen, Jingqiu Zhou, Jie Dai, Wenhao Zhang, Zhuo Zhang.
      Immunotherapy has rapidly emerged as a transformative advancement in cancer treatment, becoming essential for managing diverse malignancies. Despite the remarkable clinical efficacy of immunotherapies, including immune checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR)-T cells, across various tumor types, patient responses remain heterogeneous, with some tumors developing resistance through immune evasion strategies. Presently, the investigation of cell death mechanisms is gaining momentum as a promising avenue for immunotherapy optimization. Recent studies underscore that integrating cell death pathways with immunotherapy can significantly amplify anti-tumor immune responses. Ammonia, a metabolic byproduct within the tumor microenvironment (TME), has garnered increasing interest. Specifically, emerging research suggests that ammonia, accumulating in effector T cells as a result of glutamine metabolism, induces cell death. This distinct form of cell death, termed "ammonia death," diverges from previously characterized mechanisms. This review examines the metabolic role of glutamine in various TME cells, explores the potential regulatory links between glutamine metabolism and ammonia-induced cell death, and evaluates the feasibility of targeting ammonia-induced cell death to enhance anti-tumor immunity and improve immunotherapy outcomes.
    Keywords:  CD8+ T cell; ammonia death; glutamine; immunotherapy; tumor microenvironment
    DOI:  https://doi.org/10.3389/fimmu.2025.1643017
  12. Front Immunol. 2025 ;16 1655176
    Tumor-infiltrating lymphocytes and tumor-associated macrophages in cancer immunoediting: a targetable therapeutic axis.
    Sumon Mukherjee, Ahana Ghosh, Sourio Chakraborty, Udit Basak, Sumoyee Mukherjee, Tanya Das, Gaurisankar Sa.
      Immunotherapy has transformed the landscape of cancer treatment, offering hope to patients who were once considered beyond the reach of effective care. However, its success is restricted to a limited fraction of patients. This discrepancy in response is largely due to the complex and dynamic nature of the tumor immune-microenvironment. At the heart of this complexity is the concept of cancer immunoediting-a dynamic process through which the immune system both sculpts and is shaped by the tumor. This process unfolds in three key stages: Elimination, Equilibrium, and Escape, each representing a shifting balance between immune defenses and tumor adaptation. Central to this interaction are tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs). TILs are frontline defenders in targeting tumor cells, while TAMs can either hinder or facilitate tumor growth based on their polarization. As cancer progresses, immune selection pressure induces phenotypic alterations that promote immune evasion, fostering an environment detrimental to effective immune response. This review explores the role of these immunological components in each phase of immunoediting and their impact on the efficacy or failure of immunotherapy. Gaining deeper insight into these interactions is crucial for developing advanced immunotherapies that reshape tumor microenvironment and expand the reach of immunotherapy to more patients.
    Keywords:  TAM; TIL; immunoediting; immunotherapy; tumor microenvironment
    DOI:  https://doi.org/10.3389/fimmu.2025.1655176
  13. Redox Rep. 2025 Dec;30(1): 2564593
    Recent advances in the investigation of the regulatory network underlying reactive nitrogen species-mediated tumorigenesis: molecular mechanisms and targeted therapeutic strategies.
    Yimao Wu, Zichang Chen, Xiaoyan Chen, Yinting Hu, Yunqi Ma.
      Reactive nitrogen species (RNS) play a pivotal role in tumorigenesis through complex regulatory networks within the tumor microenvironment (TME). This review summarizes recent advances in understanding RNS-mediated mechanisms, focusing on core components and their concentration-dependent bidirectional effects on tumor cell proliferation, apoptosis, invasion, and metabolism. It explores RNS sources in the TME, including autonomous synthesis by tumor cells and secretion by immune cells (e.g., TAMs, TANs), and their modulation of key signaling pathways (e.g., PI3 K/Akt, NF-κB, HIF-1α). Additionally, the review discusses RNS-mediated regulation of immune responses and angiogenesis, highlighting their dual roles in promoting tumor progression and enabling immune evasion. Finally, it outlines potential clinical applications, such as RNS-targeted diagnostic probes and therapeutic strategies (e.g., iNOS inhibitors, NO donors), providing a foundation for precision oncology.
    Keywords:  Reactive nitrogen species; molecular mechanisms; nitric oxide; targeted therapy; tumor microenvironment; tumorigenesis
    DOI:  https://doi.org/10.1080/13510002.2025.2564593
  14. Medicine (Baltimore). 2025 Sep 26. 104(39): e44831
    Neutrophils and cancer immunotherapy: Potential mechanisms and challenges in breast cancer - a narrative review.
    Emmanuel Ifeanyi Obeagu.
      Neutrophils, the most abundant white blood cells in circulation, are gaining recognition for their intricate roles in cancer biology, particularly in breast cancer. These cells can exhibit dual behavior, either promoting tumor progression through immunosuppressive mechanisms or combating cancer by enhancing anti-tumor immune responses. Tumor-associated neutrophils (TANs) are highly plastic, with their phenotype and function influenced by the tumor microenvironment. This duality underscores the complexity of targeting neutrophils for therapeutic purposes in breast cancer immunotherapy. Key mechanisms such as neutrophil extracellular traps (NETs) and immune modulation by TANs are central to their role in breast cancer. NETs contribute to cancer metastasis by facilitating tumor cell adhesion and immune evasion, while TANs can suppress cytotoxic T-cell activity through the release of immunosuppressive mediators like arginase-1 and reactive oxygen species (ROS). Empirical studies have demonstrated that high neutrophil-to-lymphocyte ratios and excessive NET formation are correlated with poor prognosis in breast cancer patients, particularly those with aggressive subtypes such as triple-negative breast cancer.
    Keywords:  breast cancer; cancer immunotherapy; neutrophil extracellular traps; neutrophils; tumor microenvironment
    DOI:  https://doi.org/10.1097/MD.0000000000044831
  15. Cell Biol Int. 2025 Sep 29.
    Matter of Fat: Cancer-Associated Adipocytes as Mediators of Tumor Progression and Immune Evasion.
    Niti Sureka, Shikhar Chohan, Samreen Zaheer, Durre Aden, Sana Ahuja, Amit H Agravat, Seema Goel, Jaseem Hassan, Laltlanzovi Chawgthu, Hage Nobin, Sufian Zaheer.
      Peritumoral adipocytes that exhibit changes in their phenotype and distinct biological characteristics, such as reduced expression of mature adipocyte differentiation markers, increased secretion of adipocyte-derived factors, and facilitation of metabolic reprogramming in cancer cells, are referred to as cancer-associated adipocytes (CAAs). CAAs are increasingly recognized as important contributors to tumor initiation, progression, and metastasis within the tumor microenvironment (TME). Found predominantly in fat-rich tissues such as breast, ovarian, colorectal, and pancreatic cancers, CAAs undergo significant functional changes when exposed to cancer cells. These changes include lipid transfer to cancer cells, secretion of pro-inflammatory cytokines, and remodeling of the extracellular matrix, all of which enhance cancer cell survival, proliferation, and invasion. The TME, composed of various non-cancerous cells, extracellular matrix components, and signaling molecules, plays a dynamic role in influencing tumor behavior and treatment response. CAAs engage in a reciprocal interaction with cancer cells, transforming from normal adipocytes to tumor-promoting cells while simultaneously driving cancer aggressiveness. Understanding the mechanisms through which CAAs contribute to cancer progression offers promising avenues for novel therapeutic strategies targeting the TME to combat cancer more effectively.
    Keywords:  cancer associated adiopocytes; pre‐adipocyrtes; tumor microenvironment
    DOI:  https://doi.org/10.1002/cbin.70085
  16. Front Immunol. 2025 ;16 1648432
    Bridging the gap: ferroptosis of immune cells in the tumor microenvironment.
    Weijing Wang, Huiyao Li, Shuai Liang, Yani Hu, Junli Ding, Xi Wu, Dong Hua.
      Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, is increasingly recognized as a pivotal immunomodulatory mechanism within the tumor microenvironment (TME). Beyond its well-established role in tumor cell elimination, emerging evidence reveals that immune cell subsets exhibit distinct susceptibility to ferroptosis, with profound consequences for antitumor immunity. This review systematically delineates the dual and cell-type-specific roles of ferroptosis across innate and adaptive immune populations: while ferroptosis-mediated depletion of immunosuppressive cells potentiates antitumor responses, immunostimulatory cells critically depend on ferroptosis defense pathways to sustain their survival and function-their dysfunction exacerbates immune evasion. We further decode the metabolic and signaling networks that govern immune cell ferroptosis and their dynamic interplay with immunotherapy and engineered nanomaterials. Finally, we critically addressed key challenges in clinical translation, including biomarker development, cell-specific delivery, and design of nanomaterials to minimize off-target effects. By elucidating the immune context-dependence of ferroptosis, this review provides a framework for developing precision therapies that harness ferroptosis-immune crosstalk to improve cancer therapy in the clinic.
    Keywords:  ferroptosis; immune cells; immunotherapy; nanomaterials; tumor microenvironment
    DOI:  https://doi.org/10.3389/fimmu.2025.1648432
  17. Biomaterials. 2025 Sep 23. pii: S0142-9612(25)00648-9. [Epub ahead of print]327 123729
    Multifunctional exosome-driven tumor immunotherapy sensitization: converting intratumoral bacteria into antitumor fighters.
    Xiaoqing Wei, Yongxin Zhang, Yuxin Chen, Zhongzhu Mo, Bin Jiang, Jingya Zhao, Shaobing Zhou.
      Utilizing intratumoral bacteria to reprogram tumor-associated macrophages (TAMs) into a tumoricidal M1 phenotype holds great potential in cancer immunotherapy. However, intratumoral bacteria cunningly hide inside tumor cells to evade the surveillance of TAMs. Herein, we utilize dead tumor cells as bridges to connect TAMs with intratumoral bacteria. We constructed a multifunctional exosome loaded with ferroptosis inducer Fe3O4 nanoparticles and photothermal agent ICG to convert intratumoral bacteria into antitumor fighters to achieve tumor immunotherapy sensitization: 1) The multifunctional exosomes enable a synergistic enhancement of ferroptosis and photothermal therapy, efficiently inducing the death of tumor cells and intratumoral bacteria. 2) The killed tumor cells not only exhibit enhanced immunogenicity, but also promote the phagocytosis of hidden bacteria by macrophages when combined with CD47 blockade. 3) The engulfed bacteria could serve as antitumor fighters to polarize TAMs into tumoricidal M1 phenotype. The immunotherapy sensitization driven by the multifunctional exosomes provokes a robust antitumor immunity, promotes the intratumoral infiltration of T cells, and ultimately results in effective suppression of both tumor growth and metastasis.
    Keywords:  Antitumor; Exosome; Immunotherapy; Intratumoral bacteria; Tumor-associated macrophage
    DOI:  https://doi.org/10.1016/j.biomaterials.2025.123729
  18. Macromol Rapid Commun. 2025 Sep 30. e00546
    pH-Triggered Cell Surface Anti-Hapten Antibody Recruitment by Amphiphilic Block Copolymers Containing Ionizable Amines and Haptens in the Hydrophobic Block.
    Haixia Peng, Benoit Louage, Jamie De Baere, Lutz Nuhn, Bruno G De Geest.
      Cancer progression often results from immune evasion mechanisms within the tumor microenvironment (TME). Therapeutic interventions leveraging the immune system's molecular tools, such as monoclonal antibodies (mAbs), have revolutionized oncological treatments by enhancing immune responses against cancer cells. However, the efficacy of mAbs is limited by the specificity of tumor antigens. Here, we introduce a novel class of pH-sensitive antibody-recruiting molecules based on amphiphilic block copolymers. These copolymers, containing pH-responsive azepanyl motifs, undergo micelle-to-unimer transitions under mildly acidic conditions characteristic of solid tumors. Functionalized with dinitrophenol (DNP) hapten motifs, these polymers facilitate electrostatic interactions with cell surfaces in the acidic TME, enabling targeted recruitment of anti-DNP antibodies. Our findings demonstrate pH-dependent nanoparticle formation, enhanced cellular association at acidic pH, and selective antibody recruitment, warranting further investigations for tumor-targeted immunotherapy independent of specific tumor antigens.
    Keywords:  antibodies; block copolymers; immune therapy; stimuli‐responsive
    DOI:  https://doi.org/10.1002/marc.202500546
  19. Biochim Biophys Acta Rev Cancer. 2025 Sep 26. pii: S0304-419X(25)00205-7. [Epub ahead of print] 189463
    The mechanical landscape of cancer: Exploring mechanical characteristics-based therapeutic approaches.
    Hongdan Chen, Yinde Huang, Supeng Yin, Chong Li, Fan Zhang.
      Tumor mechanical alterations have emerged as a critical but underexplored marker of cancer. Cells within the tumor microenvironment (TME) are constantly exposed to matrix remodeling, aberrant shear stress, cytoskeletal tension, and tumor thrombi, all of which modulate tumor progression, therapy resistance, and stromal remodeling. This review summarizes recent advances in understanding how mechanical cues regulate tumor behavior through mechanotransduction pathways, and evaluates therapeutic strategies targeting extracellular matrix (ECM) stiffness, cytoskeletal contractility, ion channels, and physical interventions. While these approaches demonstrate translational promise, most studies remain descriptive, and major challenges, including off-target effects, limited drug penetration, and biomarker validation, continue to impede clinical application. We highlight the emerging concept of "tumor mechanomics", which integrates biomechanical fingerprints with molecular and clinical data, offering a framework for developing predictive biomarkers and guiding precision oncology.
    Keywords:  Mechanical characteristics; Mechanotransduction; Therapeutic strategies; Tumor mechanical microenvironment; Tumor progression
    DOI:  https://doi.org/10.1016/j.bbcan.2025.189463
  20. Methods Mol Biol. 2026 ;2959 97-103
    In Vitro Model for Studying Interaction of Immune Cells and Cancer Cells.
    Thanh Hoa Vo, Amie Menton, Orla O'Donovan, Edel A McNeela, Jai Prakash Mehta, Sweta Rani.
      The tumor microenvironment (TME) is a complex environment composed of a variety of cell types including cancer cells, endothelial cells, and immune cells. Cross talk between the cells in TME plays a central role in tumor growth, progression, metastasis, and response to therapy. Coculture is a method to study the interaction between various types of cells in vitro and provides a way to mimic the in vivo conditions. Two or more types of cells can be cultured in a way that, they are in direct contact with each other (direct coculture) or, separated while still communicating through the secretion of soluble factors (indirect coculture). In this chapter, we focus on indirect coculture, specifically studying the modulation of immune cells by breast cancer lines through paracrine signaling. Cells are grown in transwells that allow the transfer of soluble factors but prevent cell-to-cell contact. This model helps us understand the effects of soluble factors on both immune cells and cancer cells.
    Keywords:  Cancer; Coculture; Immune cells; Indirect coculture; Migration; Paracrine signaling; Transwells
    DOI:  https://doi.org/10.1007/978-1-0716-4734-9_7
This page is being maintained by Thomas Krichel. It was last updated on 2025‒10‒05 at 7:15.