The major bottleneck of immune checkpoint blockade therapy is its low response rate in most cancers, with a range of 10%–30%.6 For some major cancer types such as colorectal cancer with microsatellite stability, anti-PD-1/PD-L1 therapy shows nearly no effect.8 Mechanisms of non-responsiveness have been extensively studied, and many factors have been found to be relevant, such as tumor mutational burden, PD-L1 expression level, IFN signaling and MHC-I loss.9–12 However, biomarkers that faithfully predict efficacy are still lacking. The gene discussed is CD274; the disease is neoplasm.