Targeting TIGIT for cancer immunotherapy: recent advances and future directions

Abstract

As a newly identified checkpoint, T cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif (ITIM) domain (TIGIT) is highly expressed on CD4+ T cells, CD8+ T cells, natural killer (NK) cells, regulatory T cells (Tregs), and tumor-infiltrating lymphocytes (TILs). TIGIT has been associated with NK cell exhaustion in vivo and in individuals with various cancers. It not only modulates NK cell survival but also mediates T cell exhaustion. As the primary ligand of TIGIT in humans, CD155 may be the main target for immunotherapy due to its interaction with TIGIT. It has been found that the anti-programmed cell death protein 1 (PD-1) treatment response in cancer immunotherapy is correlated with CD155 but not TIGIT. Anti-TIGIT alone and in combination with anti-PD-1 agents have been tested for cancer immunotherapy. Although two clinical studies on advanced lung cancer had positive results, the TIGIT-targeted antibody, tiragolumab, recently failed in two new trials. In this review, we highlight the current developments on TIGIT for cancer immunotherapy and discuss the characteristics and functions of TIGIT.

Many Faces of Regulatory T Cells: Heterogeneity or Plasticity?

“…In addition, targeting the co-inhibitory receptors TIGIT, LAG-3 and TIM-3 is also being explored as an immunotherapeutic approach. Anti-TIGIT treatment has been shown to decrease or deplete Tregs and reduce their suppressive activity, thereby contributing to anti-tumor immunity [ 201 , 202 ]. Administration of anti-LAG-3 mAb has also been shown to reduce the number of Tregs [ 203 ].…”

“… [ 45 ] TIGIT Anti-TIGIT mAb Inhibition of TIGIT results in a decrease in or depletion of intra-tumoral Tregs and in a decrease in their suppressive function. [ 201 , 202 ] LAG-3 Anti-LAG-3 mAb Blockade of LAG-3 leads to reduction in Tregs. [ 203 ] Autoimmune and inflammatory diseases CD25 Low-dose IL-2 Elevated expression in in vivo expanded Tregs.…”