Autophagic Mechanism in Anti-Cancer Immunity: Its Pros and Cons for Cancer Therapy

Abstract

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.

Vortioxetine induces apoptosis and autophagy of gastric cancer AGS cells via the PI3K/AKT pathway

“…Accumulating convincing evidence over several decades has shown that the effectiveness of anti-cancer therapies is not only caused by apoptosis, but also involves autophagy [37,38]. Therefore, detecting autophagy-associated regulators may be a potential strategy for cancer therapy.…”

Autophagy mediates glucose starvation-induced glioblastoma cell quiescence and chemoresistance through coordinating cell metabolism, cell cycle, and survival

“…The mechanisms underlying the roles of autophagy in cancer and cancer treatment remain poorly defined 28 , 37 , 38 . What is increasingly clear is that the mechanisms are likely complex, dynamic, and context-dependent.…”

“…What is increasingly clear is that the mechanisms are likely complex, dynamic, and context-dependent. Diverse pathways and processes can come into play including autophagy-mediated effects on cell death, cell cycle arrest, tumor promoting inflammation, tumor microenvironments, immunogenicity, immune cell cytotoxicity, and checkpoints 28 , 37 , 38 . In the present study, we hoped to utilize in vitro modeling systems to elucidate the cell autonomous mechanisms in an unbiased manner through combining RNA-seq analysis with TCGA data mining.…”

Expression Analysis of Autophagy Related Markers LC3B, p62 and HMGB1 Indicate an Autophagy-Independent Negative Prognostic Impact of High p62 Expression in Pulmonary Squamous Cell Carcinomas

“…Moreover, autophagy itself is regulated and influenced by a large number of different proteins and embedded in a variety of molecular networks, pathways, and biological processes [ 7 , 10 ]. The immunology of the tumor-host interaction, for example, has been shown to interact with autophagy [ 46 ] as seen in tumors such as breast cancer [ 47 ] or melanoma [ 48 , 49 ]. Interestingly, none of the autophagy related proteins included in the present study showed an association with the density of intratumoral T lymphocytes.…”