Regulatory T cells specifically suppress conventional CD8?? 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 APCMin/+ model for microsatellite stable intestinal tumors. In this study, we investigated the effect of Treg depletion on the density and effector functions of different TCR??+ and TCR??+ T cell populations in intestinal tumors. We used the APCMin/+\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 TCR??+CD8??+ T cells was significantly increased in Treg-depleted tumors in comparison with Treg-proficient tumors. Furthermore, TCR??+CD8??+ T cells showed increased proliferation and activation as well as increased Granzyme B and IFN-? production in Treg-depleted tumors. In sharp contrast, the densities and effector functions of TCR??+CD8??+ T cells and TCR??+ T cells remained unchanged by Treg depletion. We also documented a distinct population of IL-17A+TNF+ TCR??+CD8- T cells in tumors, which were not affected by Treg depletion. We conclude that Treg depletion affects only conventional TCR??+CD8??+ 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.

SUBMITTER: Szeponik L 

PROVIDER: S-EPMC7303072 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature