ERN1 and cancer: While in hepatocellular carcinoma the regulation of PD-L1 by SIRT7 is dependent on MEF2D-mediated histone acetylation at the promoter region of CD274, the up-regulation of PD-L1 induced by SIRT7 is related to the activation of IRE1α-XBP1 axis and XBP1-driven transcriptional activation in melanoma, which is in consistent with the previous finding in macrophages.27,55 Our data has provided evidence that XBP1s can directly bind to the promoter region of CD274 and induce its transcription, highlighting a novel linkage between stress signaling and anti-tumor immunity in cancer.