Immunogenic Cell Death and Metabolic Reprogramming in Cancer: Mechanisms, Synergies, and Innovative Therapeutic Strategies.

Immunogenic cell death (ICD) is a promising cancer therapy where dying tumor cells release damage-associated molecular patterns (DAMPs) to activate immune responses. Recent research highlights the critical role of metabolic reprogramming in tumor cells, including the Warburg effect, oxidative stress, and lipid metabolism, in modulating ICD and shaping the immune microenvironment. These metabolic changes enhance immune activation, making tumors more susceptible to immune surveillance. This review explores the molecular mechanisms linking ICD and metabolism, including mitochondrial oxidative stress, endoplasmic reticulum (ER) stress, and ferroptosis. It also discusses innovative therapeutic strategies, such as personalized combination therapies, metabolic inhibitors, and targeted delivery systems, to improve ICD efficacy. The future of cancer immunotherapy lies in integrating metabolic reprogramming and immune activation to overcome tumor immune evasion, with multi-omics approaches and microbiome modulation offering new avenues for enhanced treatment outcomes.