Circulating microRNAs predict the response to anti-PD-1 therapy in non-small cell lung cancer.

Finding reliable markers for predicting the efficacy of immunotherapy is urgently needed. We sought to investigate the association between serum microRNAs (miRNAs) and checkpoint inhibitor response in non-small cell lung cancer (NSCLC). Discovery assay with sera miRNA profiling was performed, demonstrating 27 sera miRNAs (relative fold >2, p < .05), 22 higher expressed and 5 lower expressed miRNAs, were differentially expressed in 19 responders compared to those in 27 non-responders. Further validation validated miR-93, -138-5p, -200, -27a, -424, -34a, -28, -106b, -193a-3p, and -181a were significantly higher expressed (p < .01) in an independent cohort of 17 responders vs. 17 non-responders. Longitudinally, responders had increased sera expression levels of miR-93, -138-5p, -200, -27a, -424, -34a, -28, -106b, -193a-3p, and -181a from pre-treatment to post-treatment (p < .01). More importantly, statistically significant improvement in PFS of patients was associated with the 10-high expressed miRNA pattern (median PFS of 6.25 versus 3.21 months, p < .001; hazard ratio, HR, 0.45; 95% CI, 0.25-0.76). Further OS improvement was also significantly associated with the 10-high expressed miRNA pattern in responders versus non-responders (median OS of 7.65 versus 3.2 months, p < .001, HR, 0.39; 95% CI, 0.15-0.68). In conclusion, these results demonstrated that alterations in circulating miRNAs are associated with the response and outcome in NSCLC patients treated with anti-PD1 drugs.