结直肠癌中CD8^(+)T细胞的糖酵解重编程研究进展

Research progress of glycolytic reprogramming of CD8^(+) T cells in colorectal cancer

结直肠癌(CRC)是一种高度侵袭性的恶性肿瘤,在全球范围内,其发病率和死亡率分别位居第3位和第2位。近年来,免疫检查点抑制剂(ICIs)的问世,为恶性肿瘤患者带来了新的希望。但是这些以T细胞为基础的免疫治疗仅在少数患者中有效。研究显示,肿瘤细胞和CD8^(+)T细胞之间的相互作用是影响免疫治疗疗效的关键因素。像快速增殖的肿瘤细胞一样,活化后的CD8^(+)T细胞主要依赖糖酵解维持细胞增殖和功能发挥。在肿瘤微环境(TME)中,CRC细胞通过消耗大量的葡萄糖挤压CD8^(+)T细胞的营养来源,同时伴随着乳酸等代谢毒物的产生和胞外堆积,最终导致CD8^(+)T细胞糖酵解受损,细胞逐渐丧失功能变为耗竭和衰老,阻碍有效的抗肿瘤免疫治疗。因此,深入了解肿瘤细胞与CD8^(+)T细胞糖代谢之间的相互作用,可以为研发更加有效的联合治疗提供策略。本文就此研究领域的进展做一综述。

Colorectal cancer(CRC)is a highly aggressive malignancy,ranking third in morbidity and second in mortality worldwide.In recent years,the emergence of immune checkpoint inhibitors(ICIs)has brought new hope to patients with malignant tumors.But these T cell-based immunotherapies are only effective in a small number of patients.Studies have shown that the interaction between tumor cells and CD8^(+)T cells is a key factor affecting the efficacy of immunotherapy.Like rapidly proliferating tumor cells,activated CD8^(+)T cells rely mainly on glycolysis to maintain cell proliferation and function.In the tumour microenvironment(TME),the plunder of glucose by CRC cells will compress the nutritional sources of CD8^(+)T cells,accompanied by the production and extracellular accumulation of metabolic toxins such as lactic acid,which will eventually lead to impaired glycolysis of CD8^(+)T cells,gradual loss of cell function,depletion and aging,and hinder effective anti-tumor immunotherapy.Therefore,an in-depth understanding of the interaction between tumor cells and CD8^(+)T cell glucose metabolism may provide strategies for the development of more effective combination therapy.This paper reviews the progress in this field.