Targeting autophagy to enhance cancer immunotherapy: emerging mechanisms and strategies.

Abstract

Autophagy plays a dual role in cancer, supporting tumor cell survival while influencing immune escape, which can limit the efficacy of current immunotherapies. Modulating autophagy in tumor or immune cells offers a promising strategy to overcome resistance and enhance antitumor immunity. However, a deeper mechanistic understanding of how autophagy shapes the tumor immune landscape is essential to identify selective therapeutic targets, as reviewed here. In this review, we also present the emerging approaches, including tumor-specific inhibitors, nanoparticles, and genetic tools, that aim to precisely modulate autophagy while preserving immune function. Integrating insights from immuno-oncology and cellular metabolism may accelerate the development of combinatorial strategies and facilitate clinical translation of autophagy-targeted immunotherapies.