Magrì and Germano et al. show that vitamin C (VitC)-mediated tumor control relies on the adaptive immune system. High-dose VitC delayed tumor growth in immunocompetent, but not immunocompromised, mouse models of breast, colorectal, melanoma, and pancreatic cancers in a T cell-dependent manner. VitC enhanced the efficacy of immune checkpoint blockade, induced activation and infiltration of T lymphocytes to the tumor microenvironment, and developed immunological memory. In mismatch repair-deficient tumors refractory to anti-CTLA-4 alone, the combination of VitC with anti-CTLA-4 led to complete tumor remission.
Contributed by Shishir Pant
ABSTRACT: 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.
Author Info: (1) Department of Oncology, University of Torino, 10060 Candiolo (TO), Italy. Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo (TO), Italy. (2) Department of Oncology, Universi
Author Info: (1) Department of Oncology, University of Torino, 10060 Candiolo (TO), Italy. Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo (TO), Italy. (2) Department of Oncology, University of Torino, 10060 Candiolo (TO), Italy. Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo (TO), Italy. (3) Department of Oncology, University of Torino, 10060 Candiolo (TO), Italy. Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo (TO), Italy. (4) Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo (TO), Italy. (5) Department of Oncology, University of Torino, 10060 Candiolo (TO), Italy. IFOM, The FIRC Institute of Molecular Oncology, 20139 Milan, Italy. (6) Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo (TO), Italy. (7) Department of Oncology, University of Torino, 10060 Candiolo (TO), Italy. Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo (TO), Italy. (8) Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy. (9) Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo (TO), Italy. (10) Department of Oncology, University of Torino, 10060 Candiolo (TO), Italy. Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo (TO), Italy. (11) Istituto Nazionale Genetica Molecolare INGM 'Romeo ed Enrica Invernizzi', 20122 Milan, Italy. Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy. (12) Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy. (13) Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy. (14) Department of Oncology, University of Torino, 10060 Candiolo (TO), Italy. alberto.bardelli@unito.it federica.dinicolantonio@unito.it. Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo (TO), Italy. (15) Department of Oncology, University of Torino, 10060 Candiolo (TO), Italy. alberto.bardelli@unito.it federica.dinicolantonio@unito.it. Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo (TO), Italy.
