Comparative Analysis of TIGIT/CD155 Inhibitors in Cancer: Small Molecules, Antibodies, and Emerging Modalities.

Following the rise in resistance to PD-1/PD-L1 immune checkpoint blockade therapy in patients with cancer, the TIGIT/CD155 axis has emerged as a major focus of current research. Several competitive binding inhibitors, including antibodies and small molecules targeting TIGIT or CD155, have demonstrated efficacy in suppressing tumor growth and metastasis, either in preclinical models or clinical trials. This review summarizes the expression patterns of CD155, TIGIT, and DNAM-1 across immune cell subsets, along with the downstream signaling pathways modulated by these interactions. Furthermore, it provides an analysis of predicted binding sites among relevant domains. The article also systematically catalogs current therapeutic strategies targeting the CD155/TIGIT axis in patients, including novel emerging modalities.