Interestingly, HHLA2 is often expressed more frequently than the PD-1 ligand (PD-L1) and does not overlap with PD-L1 expression in certain cancers, distinguishing the KIR3DL3/TMIGD2-HHLA2 pathway as an innovative avenue for cancer immunotherapy (Bhatt et al. 2021, Ying et al. 2022). This evidence concerns the gene HHLA2 and cancer.