HHLA2 and cancer: CD276 (encoding B7 homolog 3, B7-H3), C10orf54 (encoding V-domain Ig-containing suppressor of T cell activation, VISTA), and human endogenous retrovirus-H long terminal repeat-associating 2 (HHLA2, encoding B7-H7) (Figure 1) were found to be highly expressed in tumors from patients with CRC, indicating that these members may play important roles in CRC and account for the poor efficacy of the PD-1/PD-L1 ICB therapy for this cancer type.