High-dose vitamin C enhances cancer immunotherapy

Vitamin C promotes anticancer adaptive immunity and enhances efficacy of immune checkpoint therapy. A vitamin boost for immunotherapy Despite some controversy over the years, it is gradually becoming clear that vitamin C has some anticancer effects, albeit only when given intravenously and at sufficiently high doses. However, earlier studies evaluating the anticancer effects of vitamin C have used immunodeficient mice and therefore only examined its direct effects on tumors. By studying immunocompetent mouse models of cancer, Magri et al. determined that the vitamin’s effects were much stronger in the presence of an intact immune system and that it cooperated with checkpoint immunotherapy. These findings suggest a promising approach to combination treatment, which now needs to be tested in patients. Vitamin C (VitC) is known to directly impair cancer cell growth in preclinical models, but there is little clinical evidence on its antitumoral efficacy. In addition, whether and how VitC modulates anticancer immune responses is mostly unknown. Here, we show that a fully competent immune system is required to maximize the antiproliferative effect of VitC in breast, colorectal, melanoma, and pancreatic murine tumors. High-dose VitC modulates infiltration of the tumor microenvironment by cells of the immune system and delays cancer growth in a T cell–dependent manner. VitC not only enhances the cytotoxic activity of adoptively transferred CD8 T cells but also cooperates with immune checkpoint therapy (ICT) in several cancer types. Combination of VitC and ICT can be curative in models of mismatch repair–deficient tumors with high mutational burden. This work provides a rationale for clinical trials combining ICT with high doses of VitC.