High-dose vitamin C enhances cancer immunotherapy

Alessandro Magrì, Giovanni Germano, Annalisa Lorenzato, Simona Lamba, Rosaria Chilà, Monica Montone, Vito Amodio, Tommaso Ceruti, Francesco Sassi, Sabrina Arena, Sergio Abrignani, Maurizio D'Incalci, Massimo Zucchetti, Federica Di Nicolantonio, Alberto Bardelli

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
JournalScience Translational Medicine
Issue number532
Publication statusPublished - Feb 26 2020


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