Autophagy-Driven Cancer Immunotherapy via Tumor Immune Ecosystem Remodeling
Autophagy in cancer immunotherapy
Keywords:
Autophagy, Cancer Immunotherapy, Tumor Microenvironment, Immunogenic Cell Death (ICD), Immune Reprogramming, Tumor Immune EvasionAbstract
Autophagy is a conserved catabolic pathway essential for maintaining cellular integrity, recycling damaged organelles, and supporting metabolic adaptation during stress. Beyond its homeostatic functions, aberrant autophagy plays a critical role in cancer initiation and progression. Once viewed primarily as a tumor-suppressive mechanism linked to programmed cell death, autophagy is now recognized as a highly context-dependent process that can either inhibit or facilitate tumor development. Growing evidence demonstrates that autophagy regulates multiple cancer hallmarks, including metastasis, sustained proliferation, therapeutic resistance, and immune regulation. In this review, we explore how autophagy intersects with the immune system to remodel the tumor microenvironment (TME), highlighting its dual and often paradoxical roles. Autophagy shapes the activation, differentiation, and effector functions of both innate and adaptive immune cells, enhancing antitumor immunity while also promoting immune evasion. Major TME constituents, such as tumor-associated macrophages, cancer-associated fibroblasts, dendritic cells, natural killer cells, and cytotoxic T lymphocytes, undergo autophagy-dependent reprogramming, particularly in response to hypoxia, nutrient stress, and inflammatory cues. Notably, autophagy-driven immunogenic cell death has emerged as a promising avenue to augment cancer immunotherapies, including immune checkpoint inhibitors and adoptive cell therapies. Recent preclinical and clinical advances targeting autophagy pathways underscore new therapeutic opportunities and position autophagy modulators as emerging immunopharmacological agents. Elucidating how autophagy-mediated immune remodeling shapes the TME may enable the development of next-generation precision cancer therapies.
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