The immunomodulatory role of vitamins in tumor: Mechanisms and therapeutic implications

The tumor microenvironment (TME)-marked by hypoxia, acidosis, and nutrient scarcity-creates a metabolically restrictive niche that undermines sustained antitumor immunity. Within this niche, infiltrating immune cells could become functionally exhausted to limit the efficacy of existing immunotherapies. Recently, metabolic competition between tumor cells and immune cells for nutrients has attracted great attention in immunometabolism to explain the immune dysfunction. Notably, micronutrients, particularly vitamins, have been increasingly revealed to serve as active immunoregulatory agents rather than working solely as metabolic precursors or intermediates. In this review, we highlight the role of vitamins as immune-metabolic modulators that coordinate metabolic reprogramming, epigenetic remodeling, and signal transduction in tumor-infiltrating immune cells. We further discuss how vitamin activity is shaped by tumor-specific metabolic states, molecular forms, microbiome-dependent regulation and microenvironmental conditions, resulting in context-dependent immunological outcomes. By integrating preclinical mechanistic insights with the current landscape of clinical trials, the translational challenges arising from the pleiotropic effects of vitamins have also been evaluated. Finally, we also summarize emerging biomarker-guided and tumor-targeted intervention strategies that may help improve the therapeutic utility of vitamins and overcome immunotherapy resistance.