Regulatory T cells specifically suppress conventional CD8αβ T cells in intestinal tumors of APCMin/+ mice

Abstract 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.