Vitamin-mediated cancer immune reprogramming: Context-dependent mechanisms and translational perspectives

Figure 2 Immunomodulatory effects of vitamins within the tumor microenvironment. Vitamins modulate multiple immune-cell compartments within the tumor microenvironment. All immunomodulatory outcomes depicted are predominantly supported by tier 1 pre-clinical evidence (in vitro and mouse tumor models), unless otherwise noted. Vitamins exert anti-tumor influences via two distinct routes: The reductive regulation route that boosts intrinsic anti-tumor immune-cell function, and the oxidative-damage route in which pharmacological-dose vitamin exposure triggers reactive oxygen species-dependent tumor-cell injury. All immunomodulatory outcomes depicted are predominantly supported by tier 1 pre-clinical evidence (in vitro cell experiments and mouse tumor models), unless otherwise specified. In the reductive-regulation route, dietary or supplemented vitamins enhance anti-tumor functions of macrophages, T cells, B cells, natural killer cells and dendritic cells, collectively driving tumor-cell elimination. In the oxidative-damage route, pharmacological vitamin exposure (especially high-dose ascorbate in susceptible tumor contexts) induces oxidative stress, causing structural damage to tumor-cell proteins and organelles and promoting tumor-cell death. Corresponding human interventional evidence for most of these mechanistic observations remains limited. Corresponding human interventional evidence for most of these mechanistic observations remains limited. IL-12: Interleukin-12; TNF: Tumor necrosis factor; DC: Dendritic cell; MHC: Major histocompatibility complex; TCR: T cell receptor; LTαβ: Lymphotoxin αβ; LTβR: Lymphotoxin β receptor; RA: Retinoic acid; ICAM-1: Intercellular adhesion molecule 1; LFA-1: Lymphocyte function-associated antigen-1; NK: Natural killer; GLUT1: Glucose transporter 1.