PD-L1 expression increased by IFN-γ via JAK2-STAT1 signaling and predicts a poor survival in colorectal cancer.

Zhao, Tiancheng; Li, Yezhou; Zhang, Jiayu; Zhang, Bin

PD-L1 inhibitors are widely used in tumor immunotherapy, but their mechanism in colorectal cancer remains unclear. The present study aimed to investigate the mechanisms underlying programmed death ligand 1 (PD-L1) regulation via the interferon-γ (IFN-γ)/janus kinase (JAK)/STAT signaling pathway, and its prognostic value in patients with colorectal cancer (CRC). A cohort of 181 patients were recruited to determine the association between PD-L1 expression and CRC prognosis; the patients were newly diagnosed with colorectal adenocarcinoma and had also undergone a physical tumorectomy. Immunohistochemical staining and survival analysis were used to evaluate the predictive value of PD-L1 protein expression in CRC. Gene set enrichment analysis, RT-qPCR and western blotting, etc were performed to confirm that PD-L1 is regulated by the IFN-γ/JAK/STAT signaling pathway. PD-L1 up-regulation was more frequently observed in patients with larger tumors, positive vascular or lymphatic infiltration and a poorly differentiated stage in addition to being associated with a poor survival in patients with CRC. Following the stimulation with IFN-γ, PD-L1 expression levels were revealed to be increased via the JAK2/STAT1 signaling pathway. In conclusion, the findings of the present study indicated that the expression levels of PD-L1 may be associated with a poor prognosis in patients with CRC. In addition, the results suggested that the IFN-γ-mediated overexpression of PD-L1 in CRC cells may be regulated by the JAK2/STAT1 signaling pathway.