Regulatory T cells specifically suppress conventional CD8αβ T cells in intestinal tumors of APC(Min/+) mice

The presence of activated T cells in colorectal cancer tissues is a strong predictor of patient survival. Our previous studies have shown that regulatory T cells (Treg) are able to reduce T cell transendothelial migration in vitro and accumulation of effector T cells in intestinal tumors in vivo in the murine APC(Min/+) model for microsatellite stable intestinal tumors. In this study, we investigated the effect of Treg depletion on the density and effector functions of different TCRαβ(+) and TCRγδ(+) T cell populations in intestinal tumors. We used the APC(Min/+)\DEREG mouse model, which harbor a diphtheria toxin receptor under the control of the FOXP3 promoter, to deplete Treg in tumor bearing mice. We found that the density of conventional TCRαβ(+)CD8αβ(+) T cells was significantly increased in Treg-depleted tumors in comparison with Treg-proficient tumors. Furthermore, TCRαβ(+)CD8αβ(+) T cells showed increased proliferation and activation as well as increased Granzyme B and IFN-γ production in Treg-depleted tumors. In sharp contrast, the densities and effector functions of TCRαβ(+)CD8αα(+) T cells and TCRγδ(+) T cells remained unchanged by Treg depletion. We also documented a distinct population of IL-17A(+)TNF(+) TCRγδ(+)CD8(−) T cells in tumors, which were not affected by Treg depletion. We conclude that Treg depletion affects only conventional TCRαβ(+)CD8αβ(+) T cells in intestinal tumors, while unconventional T cells and T cells in unaffected tissue are not altered. Immunotherapies aimed at depleting Treg from tumors may thus be a viable option for reinvigoration of conventional cytotoxic T cells with a Th1 cytokine profile. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00262-020-02540-9) contains supplementary material, which is available to authorized users.