Ribavirin in cancer immunotherapies: controlling nitric oxide augments cytotoxic lymphocyte function

Neoplasia. Jan-Feb 2003;5(1):3-8. doi: 10.1016/s1476-5586(03)80011-8.


Either ribavirin (RBV) or cyclophosphamide (CY) can shift an immune response from Th2 toward a Th1 cytokine profile. CY is used in this role in various current cancer immunotherapy attempts but with mixed success. More potent and reliable immunoadjuvants and Th1 response biasing methods are needed. RBV is used today mainly to augment interferon-alpha treatment of hepatitis C. RBV shifts an immune response from Th2 toward Th1 more effectively than CY and may be a safe and useful adjuvant for current cancer immunotherapeutic efforts. RBV is thought to act by inhibition of tetrahydrobiopterin synthesis. Tetrahydrobiopterin is an essential cofactor for all known isoforms of nitric oxide synthase. Lowered nitric oxide favors Th1 development as high levels favor Th2 weighting.

Publication types

  • Review

MeSH terms

  • Animals
  • Antimetabolites / therapeutic use*
  • Humans
  • Immunotherapy*
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Ribavirin / therapeutic use*
  • T-Lymphocytes, Cytotoxic / physiology*
  • Th1 Cells / immunology
  • Th2 Cells / immunology


  • Antimetabolites
  • Nitric Oxide
  • Ribavirin
  • Nitric Oxide Synthase