CD155 and its receptors in glioma: prospects for emerging immune checkpoint inhibitors

Glioma is an aggressive brain malignancy characterized by a markedly immunosuppressive microenvironment and limited response to conventional treatments. CD155, also known as the poliovirus receptor, is frequently overexpressed in glioma and plays a key role in immune escape. By interacting with inhibitory receptors such as TIGIT and CD96, as well as the activating receptor CD226, CD155 modulates the tumor immune landscape. These interactions suppress the cytotoxic activity of T cells and natural killer (NK) cells while promoting immunoregulatory phenotypes, thereby impairing immune-mediated tumor cell elimination and supporting tumor progression. The balance among these receptor-ligand interactions is critical in determining immune outcomes. Targeting the CD155 axis has emerged as a potential therapeutic strategy. Approaches including monoclonal antibodies, bispecific antibodies, and chimeric antigen receptor (CAR)-engineered immune cells are being developed to counteract immune suppression and restore antitumor responses. This review summarizes the structural and functional features of CD155 and its associated receptors, examines their roles in glioma immune evasion, and discusses recent advances and challenges in developing therapies targeting this pathway. Modulation of CD155-related signaling may offer new opportunities to improve treatment outcomes in glioma.