Regulatory T cells specifically suppress conventional CD8 αβ T cells in intestinal tumors of APC Min/+ mice

In this study, we investigated the effect of Treg depletion on the density and effector functions of different TCR αβ+ and TCR γδ+ 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 αβ+CD8 αβ+ T cells was significantly increased in Treg-depleted tumors in comparison with Treg-proficient tumors. Furthermore, TCR αβ+CD8 αβ+ 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+CD8 αα+ T cells and TCR γδ+ T cells remained unchanged by Treg depletion. We also documented a distinct population of IL-17A+TNF+ TCR γδ+CD8− T cells in tumors, which were not affected by Treg depletion. We conclude that Treg depletion affects only conventional TCR αβ+CD8 αβ+ 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.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research