Subsets of interferon signaling predict response to immune checkpoint blockade in melanoma patients.

Pre-treatment STAT1 levels were higher in responders to ICIs (CR/PR/SD for > 6 months) than in non-responders (SD < 6 months/PD). Higher pre-treatment STAT1 levels were associated with improved survival after ICIs in both the discovery and validation cohorts. Western blot analysis of human melanoma cell lines stimulated with IFN demonstrated distinct patterns of upregulation of STAT1 compared with pSTAT1Y701 and PD-L1. When combining STAT1 and PD-L1 markers, patients with STAT1highPD-L1low tumors had improved survival compared with those with STAT1lowPD-L1high tumors. >Conclusions: STAT1 may better predict melanoma response to ICIs than current strategies, and combined STAT1 and PD-L1 biomarkers may provide insight into IFN-responsive versus IFN-resistant states.