Xinjie Lu* Pages 1851 - 1865 ( 15 )
Background: T-cell immunoglobulin (Ig)-domain and mucin-domain (TIM) proteins represent a family of receptors expressed on T-cells that play essential cellular immunity roles. The TIM proteins span across the membrane belonging to type I transmembrane proteins. The N terminus contains an Ig-like V-type domain and a Ser/Thr-rich mucin stalk as a co-inhibitory receptor. The C-terminal tail oriented toward the cytosol predominantly mediates intracellular signaling.
Methods: This review discusses the structural features and functions of TIM-3, specifically on its role in mediating immune responses in different cell types and the rationale for TIM-3-targeted cancer immunotherapy.
Results: TIM-3 has gained significant importance to be a potential biomarker in cancer immunotherapy. It has been shown that blockade with checkpoint inhibitors promotes anti-tumor immunity and inhibits tumor growth in several preclinical tumor models.
Conclusion: TIM-3 is an immune regulating molecule expressed on several cell types, including IFNγ-producing T-cells, FoxP3+ Treg cells, and innate immune cells. The roles of TIM-3 in immunosuppression support its merit as a target for cancer immunotherapy.
T-cell immunoglobulin, cancer, Galectin-9, TIM-3, receptor, ligand.
The Mary and Garry Weston Molecular Immunology Laboratory, Thrombosis Research Institute, London, SW3 6LR