The interplay between autophagy and immunogenic cell death: nanomaterial-based strategies for cancer immunotherapy

Abstract

Cancer immunotherapy has significantly advanced the field of oncology. However, effectiveness of immunotherapy remains limited by tumor heterogeneity, immune evasion, and immunosuppressive tumor microenvironments. Immunogenic cell death (ICD) and autophagy are two interconnected biological mechanisms that play crucial roles in modulating tumor-immune interactions. ICD enhances antitumor immunity through the release of damage-associated molecular patterns (DAMPs), while autophagy affects the immunogenicity and viability of tumor cells in a context-dependent manner. Their complex interaction offers a distinctive platform to enhance immune responses and overcome resistance to immunotherapy. This review emphasizes recent advancements in using nanomaterials to regulate autophagy and ICD in cancer therapy. Various nanoplatforms, including metallic, polymeric, lipid-based, and carbon-based nanoparticles, have been engineered to deliver ICD inducers and autophagy modulators in a targeted TME-responsive manner. We discuss the underlying mechanisms, therapeutic synergies, and translational advantages of these dual-functioning systems. Furthermore, we address critical challenges such as biosafety, tumor specificity, and regulatory hurdles, and we explore strategies including PEGylation, biomimetic coating, and biodegradable carriers to improve clinical applications.