Predictive value of longitudinal systemic inflammatory markers for pathologic response to neoadjuvant PD-1 blockade in resectable non-small cell lung cancer.

Background: Identifying biomarkers to predict responses for neoadjuvant immunotherapy in resectable non-small cell lung cancer (NSCLC) is under intensive study. Considering the interplay between cancer, inflammation, and immunosuppression, we hypothesized that circulating and imaging inflammatory markers could serve as indicators of anti-tumor immune responses, and thus conducting an exploratory study to reveal the predictive value of combining longitudinal systemic inflammatory markers in stratifying pathologic response to neoadjuvant sintilimab. Methods: We retrospectively reviewed 36 patients (29 male and seven female) with NSCLC (stage IA-IIIB) who underwent pre- and post-treatment peripheral blood tests and Results: Of the 36 enrolled patients, 13 (36.1%) exhibited MPR. ΔNLR% was a significant negative predictor of MPR (P=0.047) and negatively correlated with pathologic regression (r=-0.34, P=0.045). Pre- and post-treatment SLRs were potential negative predictors of MPR (P=0.06; P=0.055) and negatively correlated with pathologic regression (r=-0.30, P=0.07; r=-0.31, P=0.06). The high inflammatory burden group (pre-treatment SLR >0.83 and ΔNLR% >-17%) had the lowest pathologic regression (P=0.01) and the highest infiltration abundance of pre-treatment CD68 Conclusions: The combination of pre-treatment SLR and ΔNLR% demonstrates predictive value in stratifying pathologic response to neoadjuvant immunotherapy in resectable NSCLC. The high inflammatory burden group had the lowest pathologic regression and the pre-treatment immunosuppressive microenvironment with macrophage enrichment.