Treg stability and function in the tumor microenvironment

Summury : CD4⁺Foxp3⁺ regulatory T cells (Tregs) suppress antitumor immune responses and are therefore compelling targets for immunotherapy. However, the mechanisms governing Treg stability and suppressive function within the tumor microenvironment remain poorly understood. In this presentation, I will discuss recent unpublished findings. First, I will show that the tumor microenvironment promotes substantial Treg instability, as many Tregs lose Foxp3 expression. Consequently, a significant fraction of CD4⁺Foxp3⁻ T cells—typically considered conventional CD4 T cells— are actually ex-Tregs. Second, I will highlight the critical role of TNF receptor type 2 (TNFR2) expression by Tregs in regulating antitumor immunity. TNFR2 expressed on Tregs modulates local immune responses by influencing inflammatory cytokine production by effector T cells and inducible nitric oxide synthase expression by myeloid cells. Investigating Treg stability and TNFR2⁺ Tregs within tumors provides deeper insight into the mechanisms controlling antitumor immunity.