《生命科学》 2024, 36(4): 448-455
自然杀伤细胞相关的CRC免疫微环境
摘 要：
自然杀伤细胞(natural killer cell, NK 细胞) 是先天淋巴细胞的一个亚群，具有多种细胞毒性机制，可通过产生细胞因子调节免疫应答，进而杀伤病毒感染的正常细胞和肿瘤细胞。但是在肿瘤微环境中，NK细胞浸润减少，且表型发生变化，活性降低，杀伤肿瘤细胞的功能受到抑制。因此，NK 细胞是免疫治疗领域的研究热点，而免疫检查点研究显示在肿瘤中NK 细胞功能耗竭可被逆转。结直肠癌(colorectal cancer, CRC) 是一种常见的消化系统恶性肿瘤，死亡率排名第二。相比于传统的手术治疗、放化疗，免疫治疗在CRC 中取得了一定的成效。其中免疫检查点抑制剂以PD-1/PD-L1 单抗为代表，在具有微卫星不稳定性(MSI)的CRC 患者中疗效显著，但是对大多数转移性CRC 患者效果甚微。本文对CRC 微环境中的NK 细胞功能受损及其影响因素进行总结，并重点阐述免疫检查点研究新进展，以期为CRC 治疗提供新的思路。
通讯作者：郭 英 , Email:yingguo2nd@aliyun.com
Abstract:
Natural killer cells (NK cells) are a subgroup of innate lymphocytes with a variety of cytotoxic mechanisms, which can regulate immune responses by producing cytokines to kill virus-infected normal cells or tumor cells. However, in the tumor microenvironment, the low infiltration and the changed phenotype of NK cells leads to reduced activity to kill tumor cells. So NK cells are hotspots in immunotherapy, and immune checkpoints studies have shown that the depletion of NK cells in tumors can be reversed. Colorectal cancer (CRC) is the second leading cause of cancer related deaths in the world. Compared with traditional surgery, chemoradiotherapy, immunotherapy has made great breakthroughs in the treatment of colorectal cancer. Immune checkpoint inhibitors targeting PD-1/PD-L1 are effective in colorectal cancer patients with microsatellite instability (MSI), but have no remarkable efficacy in patients with metastatic colorectal cancer. In this paper, the functional impairment of NK cells in the microenvironment of colorectal cancer and its influencing factors were summarized, and the research progress of new immune checkpoints was highlighted, hoping to provide new ideas for the treatment of colorectal cancer.
Communication Author：GUO Ying , Email:yingguo2nd@aliyun.com
