Jessie Yanxiang Guo1,2,3 and Eileen White1,3,4 1Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey 08903, USA 2Department of Chemical Biology, Rutgers Ernest Mario School of Pharmacy, Piscataway, New Jersey 08854, USA 3Ludwig Princeton Branch, Ludwig Institute for Cancer Research, Princeton University, Princeton, New Jersey 08544, USA 4Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08903, USA Correspondence: epwhitecinj.rutgers.edu

Macroautophagy (autophagy hereafter) is an intracellular nutrient scavenging pathway induced by starvation and other stressors whereby cellular components such as organelles are captured in double-membrane vesicles (autophagosomes), whereupon their contents are degraded through fusion with lysosomes. Two main purposes of autophagy are to recycle the intracellular breakdown products to sustain metabolism and survival during starvation and to eliminate damaged or excess cellular components to suppress inflammation and maintain homeostasis. In contrast to most normal cells and tissues in the fed state, tumor cells up-regulate autophagy to promote their growth, survival, and malignancy. This tumor-cell-autonomous autophagy supports elevated metabolic demand and suppresses tumoricidal activation of the innate and adaptive immune responses. Tumor-cell-nonautonomous (e.g., host) autophagy also supports tumor growth by maintaining essential tumor nutrients in the circulation and tumor microenvironment and by suppressing an antitumor immune response. In the setting of cancer therapy, autophagy is a resistance mechanism to chemotherapy, targeted therapy, and immunotherapy. Thus, tumor and host autophagy are protumorigenic and autophagy inhibition is being examined as a novel therapeutic approach to treat cancer.