Cancer Cell Survival Strategies: The Collusion between Autophagy and Immune Evasion in Renal Cell Carcinoma
Abstract
This review systematically elucidates the core mechanisms and research advancements regarding the role of autophagy in immune evasion in Renal Cell Carcinoma (RCC). Accumulating evidence indicates that autophagy exhibits a typical “context-dependent” dual role in RCC pathogenesis: it may suppress tumorigenesis in early stages, while primarily promoting cell survival and immunosuppressive functions within the established tumor microenvironment (TME). Autophagy facilitates immune escape through multi-dimensional mechanisms, including the precise regulation of PD-L1 stability, degradation of MHC-I molecules and the antigenic peptide pool, remodeling of the metabolic microenvironment, induction of T cell exhaustion, and enhancement of immunosuppressive cell functions. Therapeutically, combining autophagy inhibitors with immune checkpoint inhibitors has demonstrated significant synergistic effects in preclinical studies, and several clinical trials have provided preliminary validation of its safety and efficacy. Future research should focus on integrating multi-omics technologies and advanced disease models to deeply elucidate the autophagy regulatory network, explore its crosstalk with other cell death pathways such as pyroptosis and ferroptosis, and promote the development of personalized treatment strategies based on precise stratification of autophagy activity, thereby offering new avenues to overcome immunotherapy resistance in RCC.
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