Riggan Luke, Shah Siya, O'Sullivan Timothy E
Department of Microbiology, Immunology, and Molecular Genetics David Geffen School of Medicine at UCLA Los Angeles CA USA.
Molecular Biology Institute University of California Los Angeles CA USA.
Clin Transl Immunology. 2021 Jan 10;10(1):e1238. doi: 10.1002/cti2.1238. eCollection 2021.
Natural killer (NK) cells are cytotoxic innate lymphocytes that protect against viral infection and tumor metastasis. Despite their inherent ability to kill a broad range of virally infected, stressed and transformed cells, low numbers of dysfunctional NK cells are often observed in many advanced solid human cancers. Here, we review the potential mechanisms that influence suboptimal mature NK cell recruitment and function in the tumor microenvironment (TME) of solid tumors. We further highlight current immunotherapy approaches aimed to circumvent NK cell dysfunction and discuss next-generation strategies to enhance adoptive NK cell therapy through targeting intrinsic and extrinsic checkpoints the regulate NK cell functionality in the TME. Understanding the mechanisms that drive NK cell dysfunction in the TME will lead to novel immunotherapeutic approaches in the fight against cancer.
自然杀伤（NK）细胞是具有细胞毒性的先天性淋巴细胞，可抵御病毒感染和肿瘤转移。尽管它们具有杀死多种病毒感染、应激和转化细胞的内在能力，但在许多晚期人类实体癌中，常常观察到功能失调的NK细胞数量较少。在这里，我们综述了影响实体瘤肿瘤微环境（TME）中成熟NK细胞募集和功能欠佳的潜在机制。我们进一步强调了旨在规避NK细胞功能障碍的当前免疫治疗方法，并讨论了通过靶向调节TME中NK细胞功能的内在和外在检查点来增强过继性NK细胞治疗的下一代策略。了解驱动TME中NK细胞功能障碍的机制将为对抗癌症带来新的免疫治疗方法。
