Department of Oncology, University of Torino, 10060 Candiolo (TO), Italy.
Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo (TO), Italy.
Sci Transl Med. 2020 Feb 26;12(532). doi: 10.1126/scitranslmed.aay8707.
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.
维生素 C（VitC）已知可在临床前模型中直接损害癌细胞生长，但关于其抗肿瘤疗效的临床证据很少。此外，VitC 是否以及如何调节抗肿瘤免疫反应在很大程度上尚不清楚。在这里，我们表明，需要一个完全有能力的免疫系统才能最大限度地发挥 VitC 在乳腺癌、结直肠癌、黑色素瘤和胰腺鼠肿瘤中的抗增殖作用。高剂量的 VitC 调节免疫系统细胞对肿瘤微环境的浸润，并以 T 细胞依赖的方式延迟癌症生长。VitC 不仅增强了过继转移的 CD8 T 细胞的细胞毒性活性，而且在几种癌症类型中与免疫检查点治疗（ICT）合作。VitC 与 ICT 的联合治疗在具有高突变负担的错配修复缺陷肿瘤模型中具有治愈作用。这项工作为临床试验提供了一个将 ICT 与 VitC 高剂量联合使用的理论依据。
