SETD2 is associated with diverse biological functions, such as maintenance of genomic stability,45 antiviral immune response,46 and restriction of tumor metastasis.47 SETD2 mutations are prevalent in various human tumors and are reported to be associated with tumor progression, including glioma, clear cell renal cell carcinoma, leukemia, and prostate cancer.48–51 We then investigated the impact of SETD2 gene knockout and observed that its disruption significantly upregulates both the cell surface and total PD-L1 and HLA-I expression levels with IFNγ treatment (Supplementary Fig. 8a, b). Here, SETD2 is linked to central nervous system cancer.