Potential predictive value of JAK2 expression for Pan-cancer response to PD-1 blockade immunotherapy

Abstract

Background: Recent clinical studies have shown promise for targeting programmed cell death protein-1 (PD-1) and programmed cell death ligand 1 (PD-L1) signaling in malignant tumors. However, reliable biomarkers for predicting who would benefit from anti-PD-1/PD-L1 inhibitors have not been fully elucidated. Methods: Here, patients from The Cancer Genome Atlas Pan-Cancer database (N=9,315) were classified into three groups based on the tri-sectional quantiles of their Janus kinase 2 ( JAK2 ) RNA expression levels. Sample mRNA expression of PD-L1 and mutational load, CD8A expression [representing CD8+ cytolytic T lymphocytes (CTLs)], cytolytic activity (“CYT”) expression, and viral association were compared among groups. Results: High mRNA expression and gene amplification of PD-L1 were both significantly associated with high JAK2 expression (P JAK2 expression group exhibited significantly more somatic mutations and neoantigens than did the other groups (P JAK2 expression (P Conclusions: In conclusion, high JAK2 expression was associated with high mRNA expression of PD-L1, CD8+CTLs and mutational burdens, CYT expression, and oncogenic viral infection. This comprehensive analysis demonstrated the important value of assessing JAK2 expression to predict responders to immunotherapy.