https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.765906/full
Vitamin C and Antitumor Immune Effects
In addition to the direct antitumor effect of VitC at high doses, recent studies show that the effect of VitC on immune cells can mediate indirect antitumor effects (22, 23). Interestingly, many of these effects also occur at physiologic doses of VitC. Here, we summarize what is known about the effects of VitC on immune cells with anti-tumor activity (namely NK cells, CD4 and CD8 T cells, and ?? T cells) in the context of cancer immunotherapy. We also discuss the mechanistic basis of its effect with a brief focus on potential targets in TCR signaling. A schematic overview of the influence of VitC on different immune cells is presented in Figure 2.
Interestingly, evidence is mounting that VitC can augment the effects of ICT. Recent studies showed that pharmacologic-dose VitC potentiates PD-1 blockade, resulting in increased macrophage and CD8 T-cell tumor infiltration, increased granzyme B production, and significant tumor regression (21, 22). Similarly, addition of high doses of VitC to CTLA-4 and/or PD-1/PD-L1 blockade delayed tumor growth and led to pronounced tumor regression in different tumor mouse models (23). Although mechanistic data are not completely elucidated in these studies, it is interesting that VitC treatment enhances T cell trafficking in solid tumors (97). VitC may also amplify the effects of checkpoint inhibitor therapy through its role as an epigenetic facilitator possibly increasing the expression of retroviral elements and neoantigens (22). Taken together, these studies point the way to therapeutic combination of VitC and ICT in early-phase clinical trials.