Autophagy regulation of the tumor immunity: An old housekeeper for a new function. In Cell Death - Autophagy, Necrosis and Apoptosis. (Book Chapter)

Cancer was initially thought to be just a disease of cells with deregulated gene expression. It may be more accurate to consider cancer as a disease of the microenvironment. Despite the remarkable and fairly rapid progress over the past two decades regarding the role of the microenvironment in cancer biology and treatment, our understanding of its actual contribution to cancer resistance is still poor and fragmented. Nevertheless, the microenvironment is now considered to be of critical importance during the initiation and progression of carcinogenesis since it is involved in shaping and remodeling stroma reactivity and in reprogramming phenotypic and functional plasticity. Therefore, the tumor microenvironment represents an important hallmark of cancer, and the challenge now is to better understand how the tumor microenvironment participates in the emergence of immune-resistant tumor cell variants, which appears to be the greatest impediment to successful immunotherapy. In this context, autophagy has recently emerged as a new player in regulating the antitumor immune response under hostile tumor microenvironment. In this review, we will summarize recent data describing how autophagy activation under hypoxic stress impairs the antitumor immune response. In addition, we will discuss how tumor manages to hide from the immune attack and either mounts a “counterattack” or develops resistance to immune cells. In particular, we will focus on the effect of hypoxia-induced autophagy in allowing tumor cells to outmaneuver an effective immune response and escape from immunosurveillance. It is our belief that autophagy may represent a conceptual realm for new immunotherapeutic strategies aiming to block immune escape and therefore providing rational approach to future tumor immunotherapy design