B7H4 Role in Solid Cancers: A Review of the Literature

Anti-cancer immunotherapies entirely changed the therapeutic approach to oncological patients. However, despite the undeniable success of anti-PD-1, PD-L1, and CTLA-4 antibody treatments, their effectiveness is limited either by certain types of malignancies or by the arising problem of cancer resistance. B7H4 (aliases B7x, B7H4, B7S1, VTCN1) is a member of a B7 immune checkpoint family with a distinct expression pattern from classical immune checkpoint pathways. The growing amount of research results seem to support the thesis that B7H4 might be a very potent therapeutic target. B7H4 was demonstrated to promote tumour progression in immune "cold" tumours by promoting migration, proliferation of tumour cells, and cancer stem cell persistence. B7H4 suppresses T cell effector functions, including inflammatory cytokine production, cytolytic activity, proliferation of T cells, and promoting the polarisation of naïve CD4 T cells into induced Tregs. This review aimed to summarise the available information about B7H4, focusing in particular on clinical implications, immunological mechanisms, potential strategies for malignancy treatment, and ongoing clinical trials.