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健康组织：基质细胞存在于各种器官实质周围的间隙中，通过结构的支撑和分泌一些生长因子，帮助维持组织的完整性。如：血管内皮细胞（BECs）和周皮细胞（pericyte）的存在，可以保持血管的完整，并且保证氧气和其他营养物质可以供给到组织。细胞之间的间隙液（Interstitial fluid）是有淋巴管排出。成纤维细胞不断重塑细胞外基质（ECM）以应对结缔组织内的机械压力。肿瘤组织：肿瘤转化通常伴随着肿瘤床的形成，和周围结缔组织和基质的深刻改变，这一过程最终导致病理性肿瘤微环境的建立。促血管生成因子和抗血管生成因子之间的不平衡导致异常血管系统的形成，以大量血管渗漏为特征，还观察到基质压力增加和淋巴管引流不足。增加的流体静力负荷，以及肿瘤分泌的分子(未显示)，诱导循环间充质干细胞(MSCs)的募集，诱导激活癌症相关的成纤维细胞(CAFs)和明显的ECM积累。最后，TME中的各种趋化因子和细胞因子将活化的T细胞和髓系细胞吸引到肿瘤病变处，但弯曲的血管和致密的ECM经常阻碍它们进入肿瘤巢。尽管细胞和细胞外环境的组成可能因肿瘤类型和生长阶段而异，但越来越清楚的是，TME中细胞结构（cellular architecture）的变化可以影响肿瘤的生长、转移和耐药性。
肿瘤微环境 Tumor Microenvironment (TME)
•Immune cells
TAM，T，Treg，B，DC，NK, MDSC…
•Tumor stroma
Ø Stromal cell: Blood endothelial cells(BECs), lymphatic endothelial cells(LECs), mensenchymal cells(include: mesenchymal stem cells(MSCs) and cancer-associated fibroblasts(CAFs)) and pericytes. In some tumors, other rarer stromal cell populations, including neurons, fibrocytes, adipocytes and follicular dendritic cells.
Ø Extracelluar Matrix(ECM): A dense network of various molecules that are secreted by cells into the extracellular space. This matrix provides physical support and structure for the cells and organs in addition to serving as a reserve for important signalling molecules such as chemokines(Turley et al., 2015). CAFs are primarily responsible for ECM deposition and remodeling within the TME (Lu et al., 2012)(de Visser and Joyce, 2023). Many advanced solid tumours are desmoplastic. The principal producers of matrix within solid tumours are activated cancer-associated fibroblasts (CAFs)(Liu et al., 2019)(Cox, 2021).
•Soluble mediators
Cytokines, Chemokines, Growth factors…
肿瘤基质细胞 Tumor stromal cells
References：
Turley, S.J., Cremasco, V., and Astarita, J.L. (2015). Immunological hallmarks of stromal cells in the tumour microenvironment. Nat Rev Immunol 15, 669-682.
Lu, P., Weaver, V.M., and Werb, Z. (2012). The extracellular matrix: a dynamic niche in cancer progression. J. Cell Biol. 196, 395–406. https://doi.org/10.1083/jcb.201102147.
de Visser, K.E., and Joyce, J.A. (2023). The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth. Cancer Cell 41, 374-403.
Cox, T.R. (2021). The matrix in cancer. Nat Rev Cancer 21, 217-238.
Liu, T., Zhou, L., Li, D., Andl, T., and Zhang, Y. (2019). Cancer-Associated Fibroblasts Build and Secure the Tumor Microenvironment. Front Cell Dev Biol 7, 60.
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