CD274 and cancer: Furthermore, DNA damage activates the JAK1-signal transducer and activator of transcription 3 (STAT3) pathway, which promotes cancer cell survival and proliferation.34 Phosphorylation of STAT1/3 and Interferon Regulatory Factor 1 (IRF1) increases after DSB induction by IR, and loss of IRF1 significantly weakens PD-L1 upregulation following IR, suggesting that PD-L1 upregulation occurs via the STAT1/3-IRF1 pathway.32