TIM3⁺FOXP3⁺ regulatory T cells are tissue-specific promoters of T-cell dysfunction in cancer.

ABSTRACT: T-cell immunoglobulin mucin 3 (TIM3) is an inhibitory molecule that has emerged as a key regulator of dysfunctional or exhausted CD8⁺ T cells arising in chronic diseases such as cancer. In addition to exhausted CD8⁺ T cells, highly suppressive regulatory T cells (Tregs) represent a significant barrier against the induction of antitumor immunity. We have found that the majority of intratumoral FOXP3⁺ Tregs express TIM3. TIM3⁺ Tregs co-express PD-1, are highly suppressive and comprise a specialized subset of tissue Tregs that are rarely observed in the peripheral tissues or blood of tumor-bearing mice. The co-blockade of the TIM3 and PD-1 signaling pathways in vivo results in the downregulation of molecules associated with TIM3⁺ Treg sup

SUBMITTER: Sakuishi K 

PROVIDER: S-EPMC3654601 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature