Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital, Laboratory of Structural Immunology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China.
Department of Histology and Embryology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China.
J Exp Clin Cancer Res. 2024 Sep 28;43(1):266. doi: 10.1186/s13046-024-03195-5.
Vigorous CD8 T cells play a crucial role in recognizing tumor cells and combating solid tumors. How T cells efficiently recognize and target tumor antigens, and how they maintain the activity in the "rejection" of solid tumor microenvironment, are major concerns. Recent advances in understanding of the immunological trajectory and lifespan of CD8 T cells have provided guidance for the design of more optimal anti-tumor immunotherapy regimens. Here, we review the newly discovered methods to enhance the function of CD8 T cells against solid tumors, focusing on optimizing T cell receptor (TCR) expression, improving antigen recognition by engineered T cells, enhancing signal transduction of the TCR-CD3 complex, inducing the homing of polyclonal functional T cells to tumors, reversing T cell exhaustion under chronic antigen stimulation, and reprogramming the energy and metabolic pathways of T cells. We also discuss how to participate in the epigenetic changes of CD8 T cells to regulate two key indicators of anti-tumor responses, namely effectiveness and persistence.
在识别肿瘤细胞和对抗实体瘤方面，活性 CD8 T 细胞发挥着关键作用。T 细胞如何高效识别和靶向肿瘤抗原，以及它们如何在“排斥”实体瘤微环境中保持活性，是人们主要关注的问题。目前，人们对 CD8 T 细胞免疫轨迹和寿命的理解取得了新的进展，为设计更优化的抗肿瘤免疫治疗方案提供了指导。在这里，我们综述了增强 CD8 T 细胞对抗实体瘤功能的新方法，重点介绍了优化 T 细胞受体（TCR）表达、提高工程化 T 细胞对抗原的识别能力、增强 TCR-CD3 复合物的信号转导、诱导多克隆功能性 T 细胞向肿瘤归巢、逆转慢性抗原刺激下的 T 细胞耗竭，以及重编程 T 细胞的能量和代谢途径。我们还讨论了如何参与 CD8 T 细胞的表观遗传变化，以调节抗肿瘤反应的两个关键指标，即有效性和持久性。
