Fig. 4

The immunosuppression mechanisms underlying TIGIT action in the TME. ① TIGIT binds to D155 expressed on DCs, making DCs tolerant, resulting in increased IL-10 secretion and decreased IL-12 production. ② TIGIT acts directly on T cells independent of APCs by weakening the activation signal mediated by TCR, thereby inhibiting the T cell response ③ TIGIT and CD226 are coexpressed on T cells, and TIGIT competes with CD226 for binding their common ligand CD155, thereby directly inhibiting the T cell response and increasing the secretion rate of IL-10. ④ TIGIT directly binds to CD226 and prevents the dimerization of CD226, thereby preventing the binding of CD155 to CD226. ⑤ TIGIT expressed on Tregs binds to CD155 expressed on tumor cells or APCs, resulting in increased secretion of the Fgl2 protein, thereby inhibiting Th1/Th17 cell differentiation. ⑥ TIGIT binds to ligands and transmits inhibitory signals directly to T cells and NK cells through its cytoplasmic tail