Programmed Death-Ligand 1 (PD-L1) is an immune checkpoint molecule expressed on antigen-presenting cells and various cancer cells, critically involved in modulating T-cell-mediated immune responses. Its interaction with programmed cell death protein 1 (PD-1) on activated T cells delivers inhibitory signals that suppress cytotoxic activity and promote immune tolerance-a mechanism exploited by malignancies to evade immune surveillance. Elevated PD-L1 expression has been documented across multiple tumor types including non-small cell lung carcinoma, melanoma, and gastrointestinal cancers, correlating with advanced disease progression and poorer prognostic outcomes.
TIM-3 (T cell immunoglobulin and mucin domain 3) has been shown to mediate immune tolerance in mouse models of infectious diseases, alloimmunity, autoimmunity, and tumor Immunity. Thus, targeting TIM-3 emerges as a promising approach for further improvement of current immunotherapy. Despite a large amount of experimental data showing an immune suppressive function of TIM-3 in vivo, the exact mechanisms are not well understood. To enable effective targeting of TIM-3 for tumor immunotherapy, further in-depth mechanistic studies are warranted. These studies will also provide much-needed insight for the rational design of novel combination therapy with other checkpoint blockers. In this review, we summarize key evidence supporting an immune regulatory role of TIM-3 and discuss possible mechanisms of action.