To compensate in part for the possible suboptimal efficacy of therapeutic antibodies, the development of low-molecular weight protein drugs or small molecules modulating PD-1/PD-L1 signaling is urgently needed, and a combination therapy of small-molecule modulators and antibody drugs may be an excellent option for the treatment of cancers through complete PD-1/PD-L1 blockade in solid tumors. This evidence concerns the gene CD274 and cancer.