Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.
Department of Gastrointestinal Surgery, Xiangya Hospital of Central South University, Changsha, China.
Cancer Immunol Immunother. 2024 May 2;73(6):115. doi: 10.1007/s00262-024-03675-9.
In the malignant progression of tumors, there is deposition and cross-linking of collagen, as well as an increase in hyaluronic acid content, which can lead to an increase in extracellular matrix stiffness. Recent research evidence have shown that the extracellular matrix plays an important role in angiogenesis, cell proliferation, migration, immunosuppression, apoptosis, metabolism, and resistance to chemotherapeutic by the alterations toward both secretion and degradation. The clinical importance of tumor-associated macrophage is increasingly recognized, and macrophage polarization plays a central role in a series of tumor immune processes through internal signal cascade, thus regulating tumor progression. Immunotherapy has gradually become a reliable potential treatment strategy for conventional chemotherapy resistance and advanced cancer patients, but the presence of immune exclusion has become a major obstacle to treatment effectiveness, and the reasons for their resistance to these approaches remain uncertain. Currently, there is a lack of exact mechanism on the regulation of extracellular matrix stiffness and tumor-associated macrophage polarization on immune exclusion. An in-depth understanding of the relationship between extracellular matrix stiffness, tumor-associated macrophage polarization, and immune exclusion will help reveal new therapeutic targets and guide the development of clinical treatment methods for advanced cancer patients. This review summarized the different pathways and potential molecular mechanisms of extracellular matrix stiffness and tumor-associated macrophage polarization involved in immune exclusion and provided available strategies to address immune exclusion.
在肿瘤的恶性进展中，存在胶原的沉积和交联，以及透明质酸含量的增加，这可能导致细胞外基质硬度的增加。最近的研究证据表明，细胞外基质通过分泌和降解的改变，在血管生成、细胞增殖、迁移、免疫抑制、细胞凋亡、代谢和化疗耐药等方面发挥着重要作用。肿瘤相关巨噬细胞的临床重要性日益得到认可，巨噬细胞极化通过内部信号级联在一系列肿瘤免疫过程中发挥核心作用，从而调节肿瘤进展。免疫疗法已逐渐成为常规化疗耐药和晚期癌症患者可靠的潜在治疗策略，但免疫排斥的存在已成为治疗效果的主要障碍，其对这些方法产生抵抗的原因仍不清楚。目前，对于细胞外基质硬度和肿瘤相关巨噬细胞极化对免疫排斥的调节机制还缺乏确切的认识。深入了解细胞外基质硬度、肿瘤相关巨噬细胞极化和免疫排斥之间的关系，将有助于揭示新的治疗靶点，并指导晚期癌症患者的临床治疗方法的发展。本综述总结了细胞外基质硬度和肿瘤相关巨噬细胞极化参与免疫排斥的不同途径和潜在分子机制，并提供了应对免疫排斥的可行策略。
