The emerging impact of autophagy on the antitumor immune response

Macroautophagy (hereafter referred to as autophagy) is a cellular degradation process involved in the recycling of damaged organelles and proteins. Occurring at the basal level, autophagy participates in maintaining homeostasis in all cells. Deregulation in this process is observed in several pathologies such as cancer. Autophagy plays a dual role as tumor suppressor or tumor promoter. Such a dual role of autophagy relies on the type, the stage, and the genetic context of the tumor. In well-established tumors, autophagy operates as a mechanism maintaining the survival of tumor cells and inducing their resistance to different anticancer therapies. Emerging new data highlight the involvement of autophagy in modulating tumor cell susceptibility to immune cell-mediated killing by various overlapping mechanisms. Tumoral autophagy is also described as a regulator of immune cell infiltration into the tumor bed. These data inspired substantial attention to develop selective autophagy inhibitors that can be used as new approaches to restore tumor immune surveillance in the context of cancer immunotherapies. This chapter will recapitulate recent findings on how autophagy activation allows tumor escape from cytotoxic immune cells and regulation of intra-tumoral infiltration by immune components. We are now facing a major challenge to develop drugs selectively inhibiting the autophagic process that can be used in combination with current cancer immunotherapeutic approaches.