Further, understanding the role of B7 proteins family of ligands (B7-H3/Cd276, B7-H4/Vtcn1, B7-H5/Vista, B7-H6/Ncr3lg1, and B7-H7/Hhla2) may give rise to novel checkpoint inhibitor therapies for IBD and CRC. Here, HHLA2 is linked to colorectal carcinoma.