Emerging Forms of Regulated Cell Death Modalities Associated with Immunogenic Cell Death and Their Translational Potential in Cancer Immunotherapy
DOI:
https://doi.org/10.62051/ryr2zs48Keywords:
Tumor immunotherapy; Immunogenic cell death; Regulated cell death; Ferroptosis; Pyroptosis; Necroptosis; Cuproptosis; Disulfidptosis; Immune checkpoint inhibitors; Tumor microenvironment.Abstract
Tumor immunotherapy has demonstrated significant clinical value in various malignancies by activating the host antitumor immune response. However, its clinical benefits are still limited by factors such as insufficient tumor immunogenicity, an immunosuppressive tumor microenvironment (TME), and acquired drug resistance. Inducing immunogenic cell death (ICD) in tumor cells can promote the release of tumor antigens, the exposure of danger signals, and antigen presentation, thereby facilitating the conversion of certain “cold” tumors into “hot” tumors and enhancing the response to immunotherapy. In recent years, the relationship between regulated cell death (RCD) and ICD has received widespread attention. Nevertheless, not all forms of RCD possess equivalent immunogenicity; different RCD modalities exhibit varying degrees of potential to induce ICD, remodel the tumor immune microenvironment, and synergize with immune checkpoint inhibitor (ICI) therapy. This review focuses on several RCD types that have been actively researched in recent years and show clear associations with ICD—including ferroptosis, pyroptosis, necroptosis, cuproptosis, and disulfidptosis—summarizing their mechanistic links to ICD, their roles in immune regulation, and their translational prospects in tumor immunotherapy. It further discusses the current challenges in the field and future research directions.
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