| First Author | Wolf Y | Year | 2020 |
| Journal | Nat Rev Immunol | Volume | 20 |
| Issue | 3 | Pages | 173-185 |
| PubMed ID | 31676858 | Mgi Jnum | J:300617 |
| Mgi Id | MGI:6503992 | Doi | 10.1038/s41577-019-0224-6 |
| Citation | Wolf Y, et al. (2020) TIM3 comes of age as an inhibitory receptor. Nat Rev Immunol 20(3):173-185 |
| abstractText | T cell immunoglobulin and mucin domain-containing protein 3 (TIM3), a member of the TIM family, was originally identified as a receptor expressed on interferon-gamma-producing CD4(+) and CD8(+) T cells. Initial data indicated that TIM3 functioned as a 'co-inhibitory' or 'checkpoint' receptor, but due to the lack of a definable inhibitory signalling motif, it was also suggested that TIM3 might act as a co-stimulatory receptor. Recent studies have shown that TIM3 is part of a module that contains multiple co-inhibitory receptors (checkpoint receptors), which are co-expressed and co-regulated on dysfunctional or 'exhausted' T cells in chronic viral infections and cancer. Furthermore, co-blockade of TIM3 and programmed cell death 1 (PD1) can result in tumour regression in preclinical models and can improve anticancer T cell responses in patients with advanced cancers. Here, we highlight the developments in understanding TIM3 biology, including novel ligand identification and the discovery of loss-of-function mutations associated with human disease. In addition, we summarize emerging data from human clinical trials showing that TIM3 indeed acts as a 'checkpoint' receptor and that inhibition of TIM3 enhances the antitumour effect of PD1 blockade. |
