The potential role of vitamin C in empowering cancer immunotherapy

Biomed Pharmacother. 2022 Feb:146:112553. doi: 10.1016/j.biopha.2021.112553. Epub 2021 Dec 20.

Abstract

Vitamin C also known as L-ascorbic acid is a nutrient naturally occurring in many fruits and vegetables and widely known for its potent antioxidant activity. Several studies have highlighted the importance of using high dose vitamin C as an adjuvant anti-cancer therapy. Interestingly, it has been shown that vitamin C is able to modulate the anti-cancer immune response and to help to overcome the resistance to immune checkpoints blockade (ICB) drugs such as cytotoxic T-lymphocyte antigen 4 (CLTA-4) and programmed cell death ligand 1 (PD-L1/PD-1) inhibitors. Indeed, it was reported that vitamin C regulates several mechanisms developed by cancer cells to escape T cells immune response and resist ICB. Understanding the role of vitamin C in the anti-tumor immune response will pave the way to the development of novel combination therapies that would enhance the response of cancer patients to ICB immunotherapy. In this review, we discuss the effect of vitamin C on the immune system and its potential role in empowering cancer immunotherapy through its pro-oxidant potential, its ability to modulate epigenetic factors and its capacity to regulate the expression of different cytokines involved in the immune response.

Keywords: Cancer therapy; Immune checkpoint blockade; Immunotherapy; Vitamin C.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Agents, Immunological / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Ascorbic Acid / pharmacology*
  • Ascorbic Acid / therapeutic use
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cytokines / drug effects
  • Dose-Response Relationship, Drug
  • Drug Resistance, Neoplasm / drug effects
  • Epigenesis, Genetic / drug effects
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology
  • Immune Checkpoint Inhibitors / therapeutic use
  • Neoplasms / drug therapy*
  • Neoplasms / physiopathology
  • Oxidative Stress / drug effects
  • T-Lymphocytes / drug effects
  • Tumor Microenvironment / drug effects

Substances

  • Antineoplastic Agents
  • Antineoplastic Agents, Immunological
  • Cytokines
  • Immune Checkpoint Inhibitors
  • Ascorbic Acid