TIGIT as an emerging immune checkpoint

Summary T cell immunoglobulin and ITIM domain (TIGIT) is an inhibitory receptor expressed on lymphocytes that was recently propelled under the spotlight as a major emerging target in cancer immunotherapy. TIGIT interacts with CD155 expressed on antigen‐presenting cells or tumour cells to down‐regulate T cell and natural killer (NK) cell functions. TIGIT has emerged as a key inhibitor of anti‐tumour responses that can hinder multiple steps of the cancer immunity cycle. Pre‐clinical studies indicated that TIGIT blockade may protect against various solid and haematological cancers. Several monoclonal antibodies (mAbs) that block the inhibitory activity of human TIGIT have been developed. Clinical trials are ongoing, investigating TIGIT blockade as a monotherapy or in combination with anti‐PD1/PD‐L1 mAbs for the treatment of patients with advanced solid malignancies. In this review, we cover our current knowledge on TIGIT, from its discovery in 2009 to its current status as a clinical target. TIGIT is an emerging immune checkpoint that inhibits immune cell responses at multiple steps of the cancer‐immunity cycle. TIGIT impairs T cell priming by dendritic cells, prevents tumour cell killing by Natural Killer cells and cytotoxic T cells, and enhances the immune suppressive activity of regulatory T cells. Consequently, TIGIT constitutes a major target in cancer immunotherapy.