Li Ying-Ying, Feun Lynn G, Thongkum Angkana, Tu Chiao-Hui, Chen Shu-Mei, Wangpaichitr Medhi, Wu Chunjing, Kuo Macus T, Savaraj Niramol
Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Int J Mol Sci. 2017 Jun 19;18(6):1297. doi: 10.3390/ijms18061297.
Autophagy, a self-eating machinery, has been reported as an adaptive response to maintain metabolic homeostasis when cancer cells encounter stress. It has been appreciated that autophagy acts as a double-edge sword to decide the fate of cancer cells upon stress factors, molecular subtypes, and microenvironmental conditions. Currently, the majority of evidence support that autophagy in cancer cells is a vital mechanism bringing on resistance to current and prospective treatments, yet whether autophagy affects the anticancer immune response remains unclear and controversial. Accumulated studies have demonstrated that triggering autophagy is able to facilitate anticancer immunity due to an increase in immunogenicity, whereas other studies suggested that autophagy is likely to disarm anticancer immunity mediated by cytotoxic T cells and nature killer (NK) cells. Hence, this contradiction needs to be elucidated. In this review, we discuss the role of autophagy in cancer cells per se and in cancer microenvironment as well as its dual regulatory roles in immune surveillance through modulating presentation of tumor antigens, development of immune cells, and expression of immune checkpoints. We further focus on emerging roles of autophagy induced by current treatments and its impact on anticancer immune response, and illustrate the pros and cons of utilizing autophagy in cancer immunotherapy based on preclinical references.
自噬是一种自我吞噬机制，据报道，当癌细胞遇到应激时，自噬作为一种适应性反应来维持代谢稳态。人们已经认识到，自噬在应激因素、分子亚型和微环境条件下对癌细胞的命运起着双刃剑的作用。目前，大多数证据支持癌细胞中的自噬是导致对现有和未来治疗产生抗性的重要机制，然而自噬是否影响抗癌免疫反应仍不清楚且存在争议。越来越多的研究表明，触发自噬能够因免疫原性增加而促进抗癌免疫，而其他研究则表明自噬可能会解除细胞毒性T细胞和自然杀伤（NK）细胞介导的抗癌免疫。因此，这种矛盾需要得到阐明。在这篇综述中，我们讨论了自噬在癌细胞本身和癌症微环境中的作用，以及它通过调节肿瘤抗原呈递、免疫细胞发育和免疫检查点表达在免疫监视中的双重调节作用。我们进一步关注当前治疗诱导的自噬的新作用及其对抗癌免疫反应的影响，并根据临床前参考文献阐述在癌症免疫治疗中利用自噬的利弊。
