Qi Tongbing, Luo Ying, Cui Weitong, Zhou Yue, Ma Xuan, Wang Dongming, Tian Xuewen, Wang Qinglu
College of Sport and Health, Shandong Sport University, Jinan, China.
Key Laboratory of Biomedical Engineering and Technology of Shandong High School, Qilu Medical University, Zibo, China.
Front Cell Dev Biol. 2022 Jul 19;10:911811. doi: 10.3389/fcell.2022.911811. eCollection 2022.
Regulatory T cells (Tregs), which execute their immunosuppressive functions by multiple mechanisms, have been verified to contribute to the tumor microenvironment (TME). Numerous studies have shown that the activation of the CBM complex/NF-κB signaling pathway results in the expression of hypoxia-inducible factor-1 (HIF-1α) and interleukin-6 (IL-6), which initiate the TME formation. HIF-1α and IL-6 promote regulatory T cells (Tregs) proliferation and migration through the MAPK/CDK4/6/Rb and STAT3/SIAH2/P27 signaling pathways, respectively. IL-6 also promotes the production of HIF-1α and enhances the self-regulation of Tregs in the process of tumor microenvironment (TME) formation. In this review, we discuss how the crosstalk between the CARMA1-BCL10-MALT1 signalosome complex (CBM complex)/NF-κB and MAPK/P27 signaling pathways contributes to the formation of the TME, which may provide evidence for potential therapeutic targets in the treatment of solid tumors.
调节性T细胞（Tregs）通过多种机制发挥免疫抑制功能，已被证实对肿瘤微环境（TME）有影响。大量研究表明，CBM复合物/NF-κB信号通路的激活会导致缺氧诱导因子-1（HIF-1α）和白细胞介素-6（IL-6）的表达，从而启动TME的形成。HIF-1α和IL-6分别通过MAPK/CDK4/6/Rb和STAT3/SIAH2/P27信号通路促进调节性T细胞（Tregs）的增殖和迁移。IL-6还促进HIF-1α的产生，并在肿瘤微环境（TME）形成过程中增强Tregs的自我调节。在本综述中，我们讨论了CARMA1-BCL10-MALT1信号体复合物（CBM复合物）/NF-κB与MAPK/P27信号通路之间的相互作用如何促进TME的形成，这可能为实体瘤治疗中的潜在治疗靶点提供证据。
