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
摘要结直肠癌(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。
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abstractsColorectal 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.
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