Department of General Surgery, Clinical Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
Department of Oncology, First Affiliated Hospital of Dalian Medical University, Dalian, China.
Front Immunol. 2024 Sep 20;15:1476904. doi: 10.3389/fimmu.2024.1476904. eCollection 2024.
A steady dysfunctional state caused by chronic antigen stimulation in the tumor microenvironment (TME) is known as CD8 T cell exhaustion. Exhausted-like CD8 T cells (CD8 Tex) displayed decreased effector and proliferative capabilities, elevated co-inhibitory receptor generation, decreased cytotoxicity, and changes in metabolism and transcription. TME induces T cell exhaustion through long-term antigen stimulation, upregulation of immune checkpoints, recruitment of immunosuppressive cells, and secretion of immunosuppressive cytokines. CD8 Tex may be both the reflection of cancer progression and the reason for poor cancer control. The successful outcome of the current cancer immunotherapies, which include immune checkpoint blockade and adoptive cell treatment, depends on CD8 Tex. In this review, we are interested in the intercellular signaling network of immune cells interacting with CD8 Tex. These findings provide a unique and detailed perspective, which is helpful in changing this completely unpopular state of hypofunction and intensifying the effect of immunotherapy.
由肿瘤微环境（TME）中慢性抗原刺激引起的稳定功能障碍状态被称为 CD8 T 细胞耗竭。耗竭样 CD8 T 细胞（CD8 Tex）表现出效应和增殖能力下降、共抑制受体生成增加、细胞毒性降低以及代谢和转录改变。TME 通过长期抗原刺激、免疫检查点上调、抑制性细胞募集和抑制性细胞因子分泌诱导 T 细胞耗竭。CD8 Tex 既可能是癌症进展的反映，也可能是癌症控制不佳的原因。当前癌症免疫疗法的成功结果，包括免疫检查点阻断和过继细胞治疗，取决于 CD8 Tex。在这篇综述中，我们对与 CD8 Tex 相互作用的免疫细胞的细胞间信号网络感兴趣。这些发现提供了一个独特而详细的视角，有助于改变这种完全不受欢迎的低功能状态，并增强免疫疗法的效果。
