![]() Thus, therapeutic targeting of TIM3 likely modulates immune responses by acting on multiple cell types. Although it was originally identified as a molecule expressed by interferon-γ (IFNγ)-producing CD4 + and CD8 + T cells 1, many other cell types, including regulatory T cells (T reg cells) 4, myeloid cells 5, natural killer (NK) cells 6 and mast cells 7, have been shown to express TIM3. Of the TIM family, TIM3 has received the most attention because of its association with the regulation of immune responses in autoimmunity and cancer. The genes encoding the TIM family are located within a genomic region that has been associated with allergy and asthma 2, towards the centromeric end of the IL4, IL5 and IL13 gene locus 3. ![]() ![]() Members of the TIM family are encoded by three genes in humans ( HAVCR1, HAVCR2 and TIMD4, encoding TIM1, TIM3 and TIM4, respectively) and eight genes in mice, located on chromosome band 5q33.2 and chromosome band 11B1.1 in humans and mice, respectively. These are characterized by a common structural organization consisting of an amino-terminal immunoglobulin variable domain (V domain) with five noncanonical cysteines, a mucin stalk, a transmembrane domain and a cytoplasmic tail. 1), is a member of the TIM family of immunoregulatory proteins. T cell immunoglobulin and mucin domain-containing protein 3 (TIM3), first discovered in 2002 (ref. 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. 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. 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. 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. 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. 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-γ-producing CD4 + and CD8 + T cells.
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