Tim-3, a negative regulator of anti-tumor immunity

T cell immunoglobulin-3 (Tim-3) was identified nearly 10 years ago as a negative regulator of IFN-γ-secreting CD4+ T helper 1 and CD8+ T cytotoxic 1 cells. Tim-3 is now classed with other inhibitory receptors, such as cytotoxic lymphocyte antigen-4 and programmed death-1 that are commonly referred to as immune checkpoint molecules. Recent studies have highlighted Tim-3 as an important player in the CD8+ T cell exhaustion that takes place in chronic immune conditions such as chronic viral infection and cancer in both humans and experimental models. In addition to its role in exhausted T cells, recent data suggest that Tim-3 can further influence cancer outcome through its action on myeloid cells and cancer stem cells.

► Tim-3 is expressed on exhausted CD8+ T cells in cancer. ► Tim-3 may influence tumor immunity through its actions on myeloid cells. ► Tim-3 is expressed on cancer stem cells and may have a role in cancer initiation. ► Tim-3 expression is enriched in T cells in tumor tissue. ► Tim-3 is an attractive immunotherapeutic candidate for clinical translation.