Department of Pathogenobiology, The Key Laboratory of Zoonosis, Chinese, Ministry of Education, College of Basic Medicine, Jilin University, Changchun, PR China.
Department of Pathogenobiology, The Key Laboratory of Zoonosis, Chinese, Ministry of Education, College of Basic Medicine, Jilin University, Changchun, PR China; The Key Laboratory for Bionics Engineering, Ministry of Education, Jilin University, Changchun, PR China; Engineering Research Center for Medical Biomaterials of Jilin Province, Jilin University, Changchun, PR China; Key Laboratory for Health Biomedical Materials of Jilin Province, Jilin University, Changchun, PR China; State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang, PR China.
Mol Immunol. 2022 Apr;144:58-70. doi: 10.1016/j.molimm.2022.02.015. Epub 2022 Feb 21.
The continuous, in-depth exploration of the occurrence and development of cancer has shown that immune cell dysfunction is closely associated with tumor progression and poor clinical prognosis. The inhibition of the effector functions of immune cells by numerous immunosuppressive factors in the tumor microenvironment (TME) promotes the progression and metastasis of malignant tumors. Natural killer (NK) cells are the main effector cells in the anti-tumor innate immune system. Dysfunctional NK cells, characterized as weakened proliferation capacity and reduced production of effector cytokines, have limited ability to kill malignant cells and inhibit tumor progression. The reversal of the dysfunctional state of NK cells and enhancement of their effector functions is a promising strategy that could improve the effectiveness of cancer immunotherapy. In order to fully use of the cytotoxic effects of NK cells and revitalize the anti-tumor potential of NK cells in tumor patients, it is necessary to learn more about the characteristics of NK cell dysfunction in TME. This will provide valuable information for the development of personalized strategies to restore anti-tumor immunity. Here, we reviewed the characteristics of dysfunctional NK cells in the TME and latest progress in research, and discussed promising immunotherapy strategies that could utilize NK cell potential for cancer immunotherapy.
不断深入探索癌症的发生和发展表明，免疫细胞功能障碍与肿瘤进展和不良临床预后密切相关。肿瘤微环境（TME）中大量免疫抑制因子抑制免疫细胞的效应功能，促进恶性肿瘤的进展和转移。自然杀伤（NK）细胞是抗肿瘤固有免疫系统的主要效应细胞。功能失调的 NK 细胞表现为增殖能力减弱和效应细胞因子产生减少，其杀伤恶性细胞和抑制肿瘤进展的能力有限。逆转 NK 细胞的功能失调状态并增强其效应功能是一种很有前途的策略，可以提高癌症免疫治疗的效果。为了充分利用 NK 细胞的细胞毒性作用并恢复肿瘤患者 NK 细胞的抗肿瘤潜能，有必要更多地了解 TME 中 NK 细胞功能障碍的特征。这将为开发个性化策略以恢复抗肿瘤免疫提供有价值的信息。在这里，我们综述了 TME 中功能失调的 NK 细胞的特征以及最新的研究进展，并讨论了有希望的免疫治疗策略，这些策略可以利用 NK 细胞的潜力进行癌症免疫治疗。
