Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, 2635 Laurel Street, Vancouver, BC V6H 3Z6, Canada.
Division of Infectious Diseases, Department of Medicine, University of British Columbia, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada.
Int J Mol Sci. 2023 Apr 27;24(9):7946. doi: 10.3390/ijms24097946.
Clear cell renal cell carcinoma (ccRCC) is a type of kidney cancer that arises from the cells lining the tubes of the kidney. The tumor immune microenvironment (TIME) of ccRCC is a complex interplay of various immune cells, cytokines, and signaling pathways. One of the critical features of the ccRCC TIME is the presence of infiltrating immune cells, including T cells, B cells, natural killer cells, dendritic cells, and myeloid-derived suppressor cells. Among these cells, CD8+ T cells are particularly important in controlling tumor growth by recognizing and killing cancer cells. However, the TIME of ccRCC is also characterized by an immunosuppressive environment that hinders the function of immune cells. Several mechanisms contribute to the immunosuppressive nature of the ccRCC TIME. For instance, ccRCC cells produce cytokines such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β), which suppress immune cell activation and promote the differentiation of regulatory T cells (Tregs). Tregs, in turn, dampen the activity of effector T cells and promote tumor growth. In addition, ccRCC cells can express programmed death-ligand 1 (PD-L1), which interacts with the programmed cell death protein 1 (PD-1) receptor on T cells to inhibit their function. In addition, other immune checkpoint proteins, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and lymphocyte activation gene 3 (), also contribute to the immunosuppressive milieu of the ccRCC TIME. Finally, the hypoxic and nutrient-poor microenvironment of ccRCC can stimulate the production of immunosuppressive metabolites, such as adenosine and kynurenine, which further impair the function of immune cells. Understanding the complex interplay between tumor cells and the immune system in the ccRCC TIME is crucial for developing effective immunotherapies to treat this disease.
透明细胞肾细胞癌（ccRCC）是一种起源于肾脏管状细胞的肾癌。ccRCC 的肿瘤免疫微环境（TIME）是各种免疫细胞、细胞因子和信号通路复杂相互作用的结果。ccRCC TIME 的一个关键特征是存在浸润免疫细胞，包括 T 细胞、B 细胞、自然杀伤细胞、树突状细胞和髓系来源的抑制细胞。在这些细胞中，CD8+T 细胞通过识别和杀死癌细胞在控制肿瘤生长方面尤为重要。然而，ccRCC 的 TIME 也具有抑制性免疫环境，这会阻碍免疫细胞的功能。几种机制导致了 ccRCC TIME 的免疫抑制特性。例如，ccRCC 细胞产生细胞因子，如白细胞介素 10（IL-10）和转化生长因子-β（TGF-β），它们抑制免疫细胞的激活并促进调节性 T 细胞（Tregs）的分化。Tregs 反过来又抑制效应 T 细胞的活性并促进肿瘤生长。此外，ccRCC 细胞可以表达程序性死亡配体 1（PD-L1），它与 T 细胞上的程序性死亡蛋白 1（PD-1）受体相互作用，抑制其功能。此外，其他免疫检查点蛋白，如细胞毒性 T 淋巴细胞相关蛋白 4（CTLA-4）和淋巴细胞激活基因 3（），也有助于 ccRCC TIME 的免疫抑制环境。最后，ccRCC 的低氧和营养贫乏的微环境可以刺激免疫抑制代谢物的产生，如腺苷和犬尿氨酸，这进一步损害免疫细胞的功能。了解肿瘤细胞与 ccRCC TIME 中免疫系统之间的复杂相互作用对于开发有效的免疫疗法来治疗这种疾病至关重要。
