bims-flamet Biomed News
on Cytokines and immunometabolism in metastasis
Issue of 2025–12–14
fourteen papers selected by
Peio Azcoaga, Biodonostia HRI
  1. Tumor Microenvironment in Glioblastoma: The Central Role of the Hypoxic-Necrotic Core.
  2. Mast cell metabolism in cancer: an underexplored frontier demanding more attention.
  3. Exosomal regulation of cellular reprogramming and polarization in the tumor microenvironment.
  4. Targeting Microbe-Mediated Macrophage Education: A Novel Paradigm in Cancer Immunotherapy.
  5. Crosstalk between cancer stem cells and myeloid-derived suppressor cells: implications for tumor progression and immunotherapy.
  6. Engineering Nanoparticles to Modulate Extracellular Matrix and Immune Components of the Tumor Microenvironment in Cancer Immunotherapy.
  7. The Effects of Vitamin D on the Breast Cancer Tumor Microenvironment.
  8. The implied dysregulated RKIP-hypoxia axis in cancer and immune evasion: Clinical implications.
  9. Metal homeostasis as a therapeutic lever: advancing metalloimmunology to remodel the tumor microenvironment and enhance cancer immunotherapy.
  10. Unraveling the dual roles of tumor-infiltrating antibodies in solid tumors: friend or foe in the tumor microenvironment?
  11. CAR T cells targeting C-C motif chemokine receptor 4 (CCR4) selectively deplete human Tregs ex vivo and in vivo.
  12. Targeting the unfolded protein response for cancer therapy: mitigating tumor adaptation and immune suppression.
  13. CD301b lectin expression in the breast tumor microenvironment augments tumor growth.
  14. Mechanical Microenvironment in Tumor Immune Evasion: Bidirectional Regulation Between Matrix Stiffness and Immune Cells and Its Therapeutic Implications.
  1. Cancer Lett. 2025 Dec 09. pii: S0304-3835(25)00788-8. [Epub ahead of print] 218216
    Tumor Microenvironment in Glioblastoma: The Central Role of the Hypoxic-Necrotic Core.
    Clara Bayona, Teodora Ranđelović, Ignacio Ochoa.
      Glioblastoma (GBM), the most aggressive and lethal primary brain tumor, is characterized by profound intratumoral heterogeneity and a hostile tumor microenvironment (TME) that drives immune evasion, therapeutic resistance, and relentless progression. Among its defining pathological features is the development of a hypoxic-necrotic core, long recognized as a hallmark of poor clinical outcome. This review synthesizes current insights into how hypoxia and necrosis act not merely as pathological markers, but as a spatiotemporal evolution engine of the GBM TME, driving metabolic adaptation, extracellular matrix (ECM) remodeling, and immune evasion. We examine how oxygen and nutrient deprivation activate hypoxia-inducible factors (HIFs), triggering cascades that promote angiogenesis, altered metabolism, and accumulation of immunosuppressive metabolites. These stressors also contribute to the recruitment and polarization of tumor-associated macrophages (TAMs) and neutrophils (TANs), expansion of myeloid-derived suppressor cells (MDSCs), and infiltration of regulatory T cells (Tregs), collectively creating an immune-excluded niche. Furthermore, hypoxia-induced ECM stiffening and degradation enhance tumor invasiveness while limiting immune cell access. By exploring the dynamic interplay between physicochemical stressors and immune modulation within the necrotic core, this review highlights the need for targeting the hypoxia-necrosis axis to overcome current therapeutic limitations. A deeper understanding of these processes will be crucial for the development of precision-targeted therapies in this highly refractory malignancy.
    Keywords:  Glioblastoma; Hypoxia; Immune System; Necrosis; Tumor Microenvironment
    DOI:  https://doi.org/10.1016/j.canlet.2025.218216
  2. Front Immunol. 2025 ;16 1693954
    Mast cell metabolism in cancer: an underexplored frontier demanding more attention.
    Barbara Frossi, Giuseppina Beatrice Scialpi, Silvia Tonon, Elena Jachetti.
      Cancer metabolism is gaining considerable attention. Tumor cells are characterized by a peculiar metabolic state to sustain the continuous demand of energy and metabolites needed for their proliferation and long-term survival. Such metabolic alterations extend beyond cancer cells, affecting multiple components of the tumor microenvironment (TME), including immune cells, stromal cells, and endothelial structures, and are influenced by both local and systemic conditions. Mast cells (MCs) are innate immune cells capable of both pro- and anti- tumorigenic functions and with the potential to modulate the activity of bystander immune cells. Nevertheless, despite their established importance in the TME, the impact of MCs in modulating cancer metabolism remains largely unexplored. This review outlines current findings regarding the metabolic conditions in the TME that modulate MC function, and, vice versa, how MC-derived metabolites can influence tumor progression, acting both on cancer and stromal cells. We focus on four main altered conditions in the TME: glucose metabolism, amino acid availability, lipid composition, and hypoxia. As studies investigating MC metabolism in cancer are limited, we also discuss relevant literature addressing how metabolic stimuli influence MC activity, as well as the effects of MC-derived metabolites on target cells, in non-cancer physiological or pathological conditions, to highlight possible mechanisms that deserve further investigation in cancer settings. Deeper investigation of MC-related metabolic networks in the TME is needed, not only to elucidate their functional modulation in response to current metabolic interventions, but also to explore their potential as therapeutic targets in the context of cancer metabolism.
    Keywords:  immunometabolism; mast cells; metabolic interventions; tumor metabolism; tumor microenvironment; tumor-stroma crosstalk
    DOI:  https://doi.org/10.3389/fimmu.2025.1693954
  3. Cancer Cell Int. 2025 Dec 08.
    Exosomal regulation of cellular reprogramming and polarization in the tumor microenvironment.
    Mobina Bayat, Parviz Shahabi, Tohid Rezaei, Javid Sadri Nahand.
      The reprogramming and polarization of cells within the tumor microenvironment (TME) are fundamental processes that critically influence the dynamics of tumor progression and response to therapy. These processes can either promote tumor evasion and metastasis or mount effective anti-tumor responses, thereby determining the overall tumor landscape. At the center of this dynamic interplay are exosomes that facilitate crucial intercellular communication by transferring bioactive molecules such as proteins, lipids, and nucleic acids. While the roles of individual TME components in cancer progression have been extensively characterized, the precise mechanisms through which the reprogramming of these elements favors tumor advancement remain inadequately elucidated. This review investigates the complex functions of exosomal signaling in the reprogramming and polarization of TME constituents, highlighting their dual capacity to orchestrate tumor-promoting and tumor-suppressing signals. This synthesis aims to elucidate how the modulation of TME cell behavior impacts cancer progression and contributes to the broader understanding of tumor biology.
    Keywords:  Cellular reprogramming; Exosomal dynamics; Intercellular communication; Polarization; TME
    DOI:  https://doi.org/10.1186/s12935-025-04105-1
  4. Biomater Res. 2025 ;29 0294
    Targeting Microbe-Mediated Macrophage Education: A Novel Paradigm in Cancer Immunotherapy.
    Rongwei Xu, Xinyuan Zhao, Xu Chen, Huixi Zhou, Li Cui.
      The tumor microenvironment (TME) is a complex ecosystem where interactions between tumor cells, immune cells, and microbes notably influence cancer progression and response to therapy. Tumor-associated macrophages (TAMs), which are crucial components of the TME, exhibit remarkable plasticity, adapting their functions in response to signals from both the tumor and its microbiota. Microbes-including bacteria, viruses, fungi, and their metabolites-modulate multiple aspects of TAM biology, from polarization and metabolism to immune modulation, thereby influencing tumor progression and immune evasion. This review focuses on the mechanisms through which microbes shape TAM responses, particularly in the context of cancer immunotherapy. Emerging therapeutic strategies leverage these microbe-TAM interactions using engineered microbes, oncolytic viruses, and microbial nanomaterials to reprogram TAMs and enhance antitumor immunity. Although formidable challenges remain, including spatial and temporal heterogeneity, mechanistic complexity, and safety concerns, these innovative approaches hold the potential to revolutionize cancer treatment. By targeting the microbe-TAM axis, this therapeutic strategy offers a promising avenue for overcoming resistance and improving the effectiveness of cancer immunotherapy.
    DOI:  https://doi.org/10.34133/bmr.0294
  5. Front Immunol. 2025 ;16 1691661
    Crosstalk between cancer stem cells and myeloid-derived suppressor cells: implications for tumor progression and immunotherapy.
    Bo Wang, Xiaoguo Zhao, Shuxin Han, Yuekang Xu, Jinyao Li.
      Cancer stem cells (CSCs) represent a small subset of tumor cells populations characterized by their ability to self-renew and differentiate. These cells are often considered resistant to chemotherapy, radiotherapy, and immunotherapy, playing a crucial role in driving tumor progression and metastasis. To evade immune attacks, CSCs utilize various genetic and epigenetic strategies that diminish immune recognition, enhance tolerance to immune-induced cytotoxicity, and foster the development of a protective immunosuppressive microenvironment. This microenvironment is shaped by a group of key immunosuppressive cells, particularly myeloid-derived suppressor cells (MDSCs), which not only directly inhibit effector T cells and natural killer (NK) cells, facilitating the immune escape of CSCs, but also significantly contribute to the maintenance of tumor cell stemness and promote their metastasis. Conversely, the developmental signals of MDSCs are also regulated by CSCs. This complex interplay between MDSCs and CSCs adds layers of complexity to the cancer-immune cycle and the associated tumor treatment strategies. Therefore, understanding the detrimental interdependence between MDSCs and CSCs to effectively impede tumor progression has become heated topic in tumor immunology. In this review, we provide a timely summary of the latest studies on the reported characteristics of CSCs and MDSCs, discuss their interconnection during tumor progression, and evaluate various immunotherapeutic strategies targeting these cell populations.
    Keywords:  cancer stem cells; immunotherapy; myeloid-derived suppressor cells; tumor immune microenvironment; tumor progression
    DOI:  https://doi.org/10.3389/fimmu.2025.1691661
  6. Biomater Res. 2025 ;29 0289
    Engineering Nanoparticles to Modulate Extracellular Matrix and Immune Components of the Tumor Microenvironment in Cancer Immunotherapy.
    Bao-Toan Dang, Khang-Yen Pham, Ai-Han Nguyen, Jongjun Park, Taeg Kyu Kwon, Jong-Sun Kang, Jee-Heon Jeong, Simmyung Yook.
      Cancer immunotherapy has emerged as a transformative strategy for treating malignancies by harnessing the body's immune system. However, its clinical efficacy is often limited by the complex and immunosuppressive nature of the tumor microenvironment (TME), which poses substantial barriers to therapeutic success. The TME comprises a variety of components, including immune cells, cancer-associated fibroblasts, abnormal vasculature, extracellular matrix, and soluble mediators that collectively support tumor progression, suppress immune surveillance, and contribute to treatment resistance and poor prognosis. Recent advances in nanotechnology have introduced engineered nanomaterials as promising tools to modulate the TME and enhance the outcomes of cancer immunotherapy. These nanomaterials can be precisely engineered to interact with specific elements of the TME, enabling localized delivery, reduced systemic toxicity, and improved therapeutic efficacy. This review provides a comprehensive overview of the role of engineered nanoparticles in targeting both cellular and noncellular components of the TME. It highlights the capacity of nanocarriers to reprogram tumor-associated immune cells, including T cells, dendritic cells, natural killer cells, and tumor-associated macrophages, as well as their ability to target cancer-associated fibroblasts, remodel tumor vasculature, degrade the extracellular matrix, and modulate immunosuppressive mediators. By exploring these multifaceted interactions, we illuminate how rationally designed nanomaterials can reshape the tumor landscape to restore immune function and enhance immunotherapeutic efficacy. Finally, the review addresses current challenges, safety considerations, and future directions necessary to translate these innovations into clinically viable therapies.
    DOI:  https://doi.org/10.34133/bmr.0289
  7. Cancers (Basel). 2025 Nov 24. pii: 3751. [Epub ahead of print]17(23):
    The Effects of Vitamin D on the Breast Cancer Tumor Microenvironment.
    Balquees Kanwal, Syeda Saba Shah, Farzana Shaheen, Mekonnen Sisay Shiferaw, Deepanshu Maurya, Yujie Li, Saranya Pounraj, Zaklina Kovacevic.
      The intricate and diverse TME within breast cancer (BC) comprises a complex amalgamation of cell populations, encompassing immune cells, cancer-associated fibroblasts, cancer stem cells and the extracellular matrix. These constituents have profound influence over tumor progression and metastasis. Vitamin D (VD) is increasingly recognized as a multifunctional hormone, with strong clinical and epidemiological evidence supporting its protective role against cancer, particularly BC. Although its anti-neoplastic effects in BC have been widely studied, few investigations have thoroughly explored its influence within the tumor microenvironment (TME). This review seeks to address that gap by clarifying the current understanding of VD's regulatory functions in the TME of BC. The pivotal anti-cancer functions of VD comprise a spectrum of activities, influencing cell cycle regulation, chemoprotection, differentiation, apoptosis, proliferation, angiogenesis, as well as having anti-metastatic and anti-invasive properties. In this review, we comprehensively outline VD's anti-cancer mechanisms within the context of the BC TME, meticulously detailing its regulatory impact on cancer-associated fibroblasts, adipocytes, immune cells, cancer stem cells, and the extracellular matrix. This unique perspective highlights the potential of using VD to re-program the TME and enhance the efficacy of current BC therapeutics.
    Keywords:  breast cancer; fibroblasts; tumor microenvironment; vitamin D
    DOI:  https://doi.org/10.3390/cancers17233751
  8. Drug Resist Updat. 2025 Nov 29. pii: S1368-7646(25)00131-1. [Epub ahead of print]85 101328
    The implied dysregulated RKIP-hypoxia axis in cancer and immune evasion: Clinical implications.
    Ryan McWhorter, Salem Chouaib, Benjamin Bonavida.
      The Raf kinase inhibitor protein (RKIP) functions as both a metastasis suppressor and immune enhancer, exerting its influence over several key oncogenic signaling pathways, including the MAPK, NF-κB, and PI3K pathways. Recent studies have highlighted a potential interplay between RKIP and hypoxia-inducible factors (HIFs), particularly in the hypoxic tumor microenvironment (TME). Hypoxia is known to reprogram cellular metabolism, enhance angiogenesis, and facilitate immune escape. Through analysis of cross-talk signaling pathways between RKIP and HIFs, we establish the presence of a dysregulated RKIP-hypoxia axis in cancer. Notably, many cancers simultaneously express low levels of RKIP and high levels of HIFs an expression pattern that strongly correlates with the emergence of immune evasion mechanisms. Herein, we report on the mechanisms by which this dysregulated axis mediates immune evasion. These include the molecular regulations of RKIP and HIFs expressions, and the low expression of RKIP and high expression of HIFs in several cancers. We report on the mechanisms underlying immune evasion by the RKIP-hypoxia axis by examining various factors intimately involved in immune evasion, such as the upregulation of PD-L1, matrix metalloproteinases (MMPs), anti-apoptotic molecules, CD47, and the enhanced frequencies of regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), tumor-associated macrophage (TAM) polarization, and decreased antigen presentation. Thus, hypoxia-induced repression of RKIP establishes a feedforward loop that sustains immune evasion and tumor aggressiveness. Therapeutically, we propose that targeting the RKIP-hypoxia axis offers a new strategy to restore immune surveillance and counteract tumor progression. We present various means to target the inhibition of hypoxia as well as the induction of RKIP. Elucidating the molecular crosstalk between RKIP and hypoxic stress responses opens a new paradigm for strategies that enhance the efficacy of immunotherapies and overcome tumor resistance.
    Keywords:  Cancer; RKIP; hypoxia; immune evasion; signaling pathways; targeted therapies
    DOI:  https://doi.org/10.1016/j.drup.2025.101328
  9. Theranostics. 2026 ;16(3): 1350-1373
    Metal homeostasis as a therapeutic lever: advancing metalloimmunology to remodel the tumor microenvironment and enhance cancer immunotherapy.
    Xin Chen, Qi Wang, Hongxia Zhang, Ye Wang, Haiying Zhu.
      Targeting the dysregulation of essential metal homeostasis represents a rapidly evolving frontier in cancer immunotherapy. The tumor microenvironment (TME) is a complex immunosuppressive ecosystem comprising tumor cells, immune cells, stromal components, extracellular matrix, and diverse cytokines/chemokines, characterized by hypoxia, acidosis, elevated redox stress, and metabolic dysregulation that drive tumor progression and immunotherapy resistance. Crucially, dysregulated homeostasis of essential metals (e.g., Cu, Fe, Zn, Mg, Mn, Ca, Cr, Na, K) pervades the TME, directly promoting tumorigenesis through oncogenic pathway activation and aberrant energy metabolism while facilitating immune evasion, amplifying immunosuppression, and undermining cancer immunotherapies. In response, recent strategies have focused on leveraging metalloimmunology to reprogram the TME via: (1) activation of innate/adaptive immunity, (2) disruption of tumor metabolism, (3) induction of programmed cell death, and (4) triggering of immunogenic cell death (ICD). These approaches synergize with existing immunotherapies to enhance efficacy, aided by nanotechnology-enabled precision delivery of metal-based agents. In conclusion, by mastering the intricate interplay between metal ions and the immunosuppressive TME, these strategies hold immense potential to remodel the TME, reinvigorate anti-tumor immunity, and ultimately enhance the efficacy of next-generation cancer immunotherapies. This review presents metalloimmunology as an integrative paradigm connecting metal biology, tumor immunology, and nanotechnology, providing a transformative outlook for immunotherapy.
    Keywords:  metal homeostasis; metalloimmunotherapy; nanomedicine; tumor microenvironment
    DOI:  https://doi.org/10.7150/thno.121988
  10. Front Immunol. 2025 ;16 1671839
    Unraveling the dual roles of tumor-infiltrating antibodies in solid tumors: friend or foe in the tumor microenvironment?
    Lingrui Miao, Run Zhou, Longfei Zhang, Linlu Feng, Yiao Wang, Pan Song, Dong Lv, Tai-Min Shen.
      Within the tumor microenvironment (TME) of solid malignancies, tumor-infiltrating antibodies, have been identified as significant modulators of tumor progression and immune response. Tumor-infiltrating antibodies predominantly secreted by plasma cells but also including a small proportion of cancer-derived antibodies. This review aims to elucidate the multifaceted roles of tumor-infiltrating antibodies in the immunology of solid tumors, focusing on their dualistic nature within the TME. This review outlines the mechanisms of B cell activation, antibody class switching, plasma cell differentiation and antibody production, with a focus on their contributions to tumor immunity in solid cancers. Additionally, we discuss the emerging potential of tumor-infiltrating antibodies as both therapeutic targets and diagnostic biomarkers, offering insights that may inform future strategies in cancer treatment. Collectively, antibody functions are shaped by their isotypes: IgG is often associated with improved prognosis in various solid tumors. IgG1 and IgG3 generally mediate anti-tumor responses via antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), while IgG4 may impair immune effector functions and associate with immune tolerance. IgM, as an early humoral responder, enhances tumor surveillance through complement dependent cytoxicity (CDC), phagocytosis, and apoptosis induction. IgA predominantly promotes tumor progression through immune suppression. IgE exhibits context-dependent pro- and anti-tumor activities, though current evidence is limited, whereas the function of IgD remains largely unknown. Additionally, tumor-derived IgG promotes tumor growth, metastasis, and immune evasion. These findings may open new avenues of research to develop targeted therapies that modulate tumor-infiltrating antibodies, potentially improving the efficacy and safety profiles of current immunotherapeutic approaches. Overall, this review focuses on tumor-infiltrating antibodies in solid tumors and does not encompass hematological malignancies, aiming to provide a more precise understanding of antibody-mediated regulation within the solid tumor microenvironment.
    Keywords:  B cells; plasma cells; solid tumors; tumor microenvironment (TME); tumor-infiltrating antibodies
    DOI:  https://doi.org/10.3389/fimmu.2025.1671839
  11. Blood Adv. 2025 Dec 10. pii: bloodadvances.2025017573. [Epub ahead of print]
    CAR T cells targeting C-C motif chemokine receptor 4 (CCR4) selectively deplete human Tregs ex vivo and in vivo.
    Caitlin M Tilsed, Karen P Fong, Xinyi Shi, Tatiana Akimova, Liqing Wang, Estela Noguera-Ortega, Ryan Krouse, Andres Bermudez, Sunil Singhal, Regina M Young, Evgeniy Eruslanov, Keisuke Watanabe, Wayne W Hancock, Carl H June, Steven Albelda.
      Regulatory T cells (Tregs) are essential for maintaining immune tolerance but also contribute to immune suppression within the tumor microenvironment (TME), dampening anti-tumor immunity in hematologic and solid tumors. As such, strategies aimed at depleting Tregs or reducing their suppressive activity are of great clinical interest. C-C Chemokine receptor 4 (CCR4) is highly expressed on intratumoral Tregs and mediates Treg migration into the TME. Although current therapies targeting CCR4 using monoclonal antibodies have shown some Treg depletion in clinical trials, their clinical efficacy has been limited. We therefore tested whether chimeric antigen receptor (CAR) T cell therapy could be used to deplete Tregs. We evaluated human-specific CCR4-directed CAR T cells (CCR4-CARTs) previously developed for T cell malignancies and determined whether these CARTs could deplete human Tregs ex vivo and in vivo. In patient-derived malignant pleural effusions and lung cancer tumor digests, CCR4 CARTs almost completely depleted Tregs, plus a small population of CCR4+ CD4+ non-Tregs, while sparing CD8+ T cells. When tested in vivo in humanized mice, a single dose of CCR4 CART led to nearly complete Treg depletion. These findings support the potential of CCR4 CARTs as a selective and effective approach to Treg modulation and warrant further clinical investigation.
    DOI:  https://doi.org/10.1182/bloodadvances.2025017573
  12. Biomark Res. 2025 Dec 11. 13(1): 156
    Targeting the unfolded protein response for cancer therapy: mitigating tumor adaptation and immune suppression.
    Bilal Unal, Fahri Saatcioglu.
      There are significant stress factors within the tumor microenvironment (TME), such as hypoxia, oxidative stress, and nutrient deprivation. These disrupt endoplasmic reticulum (ER) function in cancer cells, as well as the infiltrating immune cells, leading to activation of the unfolded protein response (UPR) signaling, which the tumor uses to mitigate stress and survive. There are three canonical UPR pathways that are regulated by respective ER-resident transmembrane sensors: inositol-requiring protein 1α (IRE1α), PKR-like ER kinase (PERK), and activating transcription factor 6 (ATF6); activation of these pathways results in expression of cognate transcription factors that regulate gene expression to mitigate ER stress. Persistent UPR activation in the TME has been linked to aberrant tumor growth, progression, metastasis, angiogenesis, and therapy resistance in different cancer types. In addition, modulation of UPR activity significantly impacts immune cell function at different levels further impacting its role on the TME. Therefore, there is now significant interest to design novel therapies that target the UPR to kill cancer cells and simultaneously enhance protective anti-tumor immunity. Here we summarize recent findings as to how targeting UPR signaling can induce tumor regression and at the same time galvanize the immune response. We discuss the potential of integrating UPR targeting with other therapies, such as immune checkpoint inhibition, highlighting emerging strategies to improve therapeutic efficacy and overcome resistance. These recent insights underscore the importance of UPR as a novel therapeutic target for cancer treatment.
    Keywords:  ATF6; Cancer; Cancer immunotherapy; Endoplasmic reticulum stress; IRE1alpha; Immune check point inhibitors; PD-1; PERK; Tumor microenvironment; Unfolded protein response
    DOI:  https://doi.org/10.1186/s40364-025-00813-y
  13. Res Sq. 2025 Dec 03. pii: rs.3.rs-8148605. [Epub ahead of print]
    CD301b lectin expression in the breast tumor microenvironment augments tumor growth.
    Ahmet Ozdilek, Amy V Paschall, Zahra Nawaz, Afaq M M Niyas, Fikri Y Avci.
      Aberrant tumor glycosylation can alter immune recognition; however, the specific influence of glycan-lectin interactions on tumor progression remains poorly understood. Here, we identify the C-type lectin receptor CD301b (encoded by Mgl2 ) as a regulator of immune activity within the breast tumor microenvironment (TME). Using a murine triple-negative breast cancer model, we demonstrate that tumors expressing the Tn glycoantigen grow more rapidly, and this growth is facilitated by CD301b⁺ immune cells. Depletion or genetic loss of CD301b markedly suppressed tumor growth, indicating that CD301b promotes tumor progression through myeloid-tumor interactions. Phenotypic analyses revealed that CD301b⁺ cells within tumors are type 2 conventional dendritic cells (cDC2s), a subset known to influence immune polarization. Single-cell RNA sequencing of human breast cancers showed that the human ortholog CLEC10A is expressed in cDC2-like dendritic cells and select macrophage subsets, suggesting a conserved role for CD301⁺ myeloid populations. Transcriptomic profiling of tumors developed in Mgl2 -deficient mice revealed a shift toward an inflammatory, immune-activated state consistent with enhanced antitumor immunity. Together, these findings establish a link between tumor glycosylation and lectin signaling of myeloid cells, highlighting CD301b as a potential target for reprogramming the tumor immune microenvironment in breast cancer.
    DOI:  https://doi.org/10.21203/rs.3.rs-8148605/v1
  14. Int J Biol Sci. 2026 ;22(1): 280-307
    Mechanical Microenvironment in Tumor Immune Evasion: Bidirectional Regulation Between Matrix Stiffness and Immune Cells and Its Therapeutic Implications.
    Jing Ai, Huayao Li, Minpu Zhang, Jingyang Liu, Lijuan Liu, Changgang Sun.
      Immune evasion remains a major obstacle to effective cancer immunotherapy. While the regulatory mechanisms of the tumor biochemical microenvironment are relatively well-characterized, the role of its mechanical microenvironment-particularly pathologically elevated matrix stiffness-in immune evasion remains to be fully elucidated. Immune cells, as dynamic responders within the tumor microenvironment, are not merely passive recipients of mechanical signals but also active participants in driving pathological matrix stiffening. This review focuses on the elevated matrix stiffness resulting from abnormal deposition and crosslinking of the tumor extracellular matrix, systematically elucidating how it impairs immune cell function and drives immune evasion through physical barriers and mechanotransduction. Additionally, we further propose an innovative concept: the "matrix stiffness-immune cell bidirectional regulatory axis." Dissecting this regulatory loop provides an essential mechanical perspective for understanding immune evasion and offers a conceptual framework for developing matrix-targeted strategies to enhance immunotherapy. By integrating current evidence, this review aims to clarify the role of this bidirectional axis and to identify novel therapeutic targets and strategies that may improve the efficacy of cancer immunotherapies.
    Keywords:  Extracellular matrix; Immune cell function; Immune evasion; Immunotherapy.; Matrix stiffness
    DOI:  https://doi.org/10.7150/ijbs.121356
This page is being maintained by Thomas Krichel. It was last updated on 2025‒12‒14 at 7:50.