State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Department of Pathology, West China Hospital, Sichuan University, Chengdu, China.
J Cell Mol Med. 2021 Mar;25(5):2333-2341. doi: 10.1111/jcmm.16331. Epub 2021 Feb 18.
Autophagy is frequently induced in the hypoxic tumour microenvironment. Accumulating evidence reveals important functions of autophagy at the tumour-immune interface. Herein, we propose an update on the roles of autophagy in modulating tumour immunity. Autophagy promotes adaptive resistance of established tumours to the cytotoxic effects of natural killer cells (NKs), macrophages and effector T cells. Increased autophagic flux in tumours dampen their immunogenicity and inhibits the expansion of cytotoxic T lymphocytes (CTLs) by suppressing the activation of STING type I interferon signalling (IFN-I) innate immune sensing pathway. Autophagy in suppressive tumour-infiltrating immune subsets maintains their survival through metabolic remodelling. On the other hand, autophagy is involved in the antigen processing and presentation process, which is essential for anti-tumour immune responses. Genetic deletion of autophagy induces spontaneous tumours in some models. Thus, the role of autophagy is context-dependent. In summary, our review has revealed the dichotomous roles of autophagy in modulating tumour immunity. Broad targeting of autophagy may not yield maximal benefits. The characterization of specific genes regulating tumour immunogenicity and innovation in targeted delivery of autophagy inhibitors into certain tumours are among the most urgent tasks to sensitize cold cancers to immunotherapy.
自噬在缺氧的肿瘤微环境中经常被诱导。越来越多的证据揭示了自噬在肿瘤免疫界面中的重要功能。在此，我们提出了自噬在调节肿瘤免疫方面的作用的最新进展。自噬促进了已建立的肿瘤对自然杀伤细胞（NK）、巨噬细胞和效应 T 细胞的细胞毒性作用的适应性抵抗。肿瘤中自噬通量的增加降低了其免疫原性，并通过抑制 STING Ⅰ型干扰素信号（IFN-I）先天免疫感应途径的激活来抑制细胞毒性 T 淋巴细胞（CTL）的扩增。在抑制性肿瘤浸润免疫细胞亚群中，自噬通过代谢重编程维持其存活。另一方面，自噬参与抗原加工和呈递过程，这对于抗肿瘤免疫反应至关重要。在某些模型中，自噬的基因缺失会诱导自发性肿瘤。因此，自噬的作用是依赖于背景的。总之，我们的综述揭示了自噬在调节肿瘤免疫中的双重作用。广泛靶向自噬可能不会带来最大的益处。目前最紧迫的任务之一是鉴定特定的基因来调节肿瘤免疫原性，并创新将自噬抑制剂靶向递送至某些肿瘤，以提高免疫疗法对冷肿瘤的敏感性。
