Immunotherapy, especially targeting immune checkpoints, such as CTLA4 or PD1/PD-L1, has been broadly approved for treating human cancers and exhibits durable clinical benefits.6,32,33 Emerging evidence suggests that PD-L1 expression levels in tumor cells might determine the clinical response to PD1/PD-L1 blockade.34,35 Hence, it is essential to understand the molecular mechanisms underlying controlling PD-L1 protein expression and stability, especially in G.C. Herein, we employed a FACS-based whole-genome CRISPR-Cas9 screen in G.C. cells to identify genes that control PD-L1 expression. The gene discussed is CD274; the disease is cancer.