Treg stability and function in the tumor environment

CD4+ Foxp3+ regulatory T cells (Tregs) inhibit antitumor responses and are attractive targets for immunotherapy. In these tumor environments, their mechanisms of suppression and their ability to lose Foxp3 and their suppressive function are still poorly defined. In this presentation, I will present recent unpublished data. Firstly, we will see the essential role of TNF receptor type 2 expression by Tregs in their ability to regulate antitumor immunity. Expressed by Tregs, TNFR2 controls antitumor immunity by acting locally on inflammatory cytokines produced by effector T cells and on iNOS produced by myeloid cells. Secondly, I will show that tumor environments are favorable to a very high Treg instability, which lose Foxp3 expression. Thus, a significant fraction of CD4+Foxp3- T cells, usually considered to be conventional T cells, are actually exTregs. Studying these exTregs should provide a better understanding of the mechanisms of antitumor immunity.