biostudies-literatureSakuishi KNIAID NIH HHSe23849https://www.ebi.ac.uk/biostudies/studies/S-EPMC3654601biostudies-literatureUnknown2(4)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 supOncoimmunologyTIM3⁺FOXP3⁺ regulatory T cells are tissue-specific promoters of T-cell dysfunction in cancer.PMC3654601P01 AI073748Sullivan JMAnderson ACTeng MWNgiow SFSakuishi KKuchroo VKSmyth MJfalseTIM3⁺FOXP3⁺ regulatory T cells are tissue-specific promoters of T-cell dysfunction in cancer.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 sup2013-01-01T00:00:00Z2013 Apr2026-05-05T05:36:34.124Z2026-04-07T21:29:36.747ZS-EPMC36546012373433110.4161/onci.23849