肿瘤细胞治疗研究
英文原题：Stromal cells in the tumor microenvironment: accomplices of tumor progression?
经过 10 余年的努力，免疫细胞在 TME 中的作用以及基于免疫细胞治疗肿瘤的策略发展迅速。
肿瘤微环境（TME）由细胞和细胞外基质（非细胞成分）组成；细胞成分包括癌细胞以及免疫细胞、基质细胞等非恶性细胞。这三类细胞在体内形成复杂信号，进一步影响肿瘤发生、发展和转移，并参与抗肿瘤治疗耐药。由于免疫检查点抑制剂（ICI）和CAR-T（CAR-T）细胞治疗实体瘤和血液系统恶性肿瘤取得显著疗效，免疫细胞成为 TME 研究的热点。经过 10 多年努力，人们对免疫细胞在 TME 中的作用及基于免疫细胞治疗肿瘤的策略有了快速发展。此外，多种肿瘤的指南已推荐 ICI 作为一线或二线治疗。与此同时，基质细胞是 TME 中另一大类细胞成分，在肿瘤代谢、生长、转移、免疫逃逸和治疗耐药中也发挥重要作用。基质细胞既可由邻近的非癌宿主基质细胞募集而来，也可通过基质细胞向基质细胞或肿瘤细胞向基质细胞的转分化形成。基质细胞可通过分泌多种因子和外泌体、参与肿瘤血管生成和代谢，以及调节 TME 免疫反应和细胞外基质，参与肿瘤发生、发展和药物耐药。然而，随着对基质细胞认识加深，人们发现基质细胞并非只促进肿瘤，在某些情况下也可抑制肿瘤。本综述将介绍 TME 中基质细胞的来源、其在肿瘤发生和发展中的作用及具体机制，以及基于基质细胞的肿瘤治疗策略；重点讨论基质细胞中的肿瘤相关成纤维细胞（CAF）、间充质干细胞（MSC）、肿瘤相关脂肪细胞（CAA）、肿瘤内皮细胞（TEC）和周细胞（PC）。
The tumor microenvironment (TME) is made up of cells and extracellular matrix (non-cellular component), and cellular components include cancer cells and non-malignant cells such as immune cells and stromal cells. These three types of cells establish complex signals in the body and further influence tumor genesis, development, metastasis and participate in resistance to anti-tumor therapy. It has attracted scholars to study immune cells in TME due to the significant efficacy of immune checkpoint inhibitors (ICI) and chimeric antigen receptor T (CAR-T) in solid tumors and hematologic tumors. After more than 10 years of efforts, the role of immune cells in TME and the strategy of treating tumors based on immune cells have developed rapidly. Moreover, ICI have been recommended by guidelines as first- or second-line treatment strategies in a variety of tumors. At the same time, stromal cells is another major class of cellular components in TME, which also play a very important role in tumor metabolism, growth, metastasis, immune evasion and treatment resistance. Stromal cells can be recruited from neighboring non-cancerous host stromal cells and can also be formed by transdifferentiation from stromal cells to stromal cells or from tumor cells to stromal cells. Moreover, they participate in tumor genesis, development and drug resistance by secreting various factors and exosomes, participating in tumor angiogenesis and tumor metabolism, regulating the immune response in TME and extracellular matrix. However, with the deepening understanding of stromal cells, people found that stromal cells not only have the effect of promoting tumor but also can inhibit tumor in some cases. In this review, we will introduce the origin of stromal cells in TME as well as the role and specific mechanism of stromal cells in tumorigenesis and tumor development and strategies for treatment of tumors based on stromal cells. We will focus on tumor-associated fibroblasts (CAFs), mesenchymal stem cells (MSCs), tumor-associated adipocytes (CAAs), tumor endothelial cells (TECs) and pericytes (PCs) in stromal cells.
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