Abstract: In recent years, the application of immune checkpoint blockade to cancer therapy has attracted widespread attention. Antibodies targeting the related receptors PD-1, PD-L1, or CTLA-4 have benefited some patients but not others in clinical trials. Identification of more immune checkpoints and exploration of their mechanisms of action will contribute to broadening the efficacy of tumor immunotherapy. Among a new generation of immune checkpoints, TIGIT, CD226, CD112R, and CD96 are a group of immunoglobulin superfamily receptors expressed by immune cells that interact with nectin and nectin-like (Nectin/Necl) molecules (CD155, CD112) expressed by tumor cells, and play a huge role in tumor immune response. In this review, the molecular structures of CD155, CD112, TIGIT, CD226, CD112R, and CD96 and their roles in tumor immune response are reviewed, and their potential application in cancer immunotherapy is discussed.