Several clinical trials have shown the safety and effectiveness of PD-1/
PD-L1 inhibitors in
neoadjuvant therapy in resectable
non-small cell lung cancer (NSCLC). However, 18-83% patients can benefit from it. In this study, we aimed to assess the association of PD-L1 expression,
tumor mutation burden, copy number alteration (CNA, including copy number gain and loss) burden with the pathologic response to neoadjuvant PD-1 blockade and investigate the changes in the
tumor immune microenvironment (TIME) during neoadjuvant
immunotherapy in NSCLC. Pre-
immunotherapy treatment
tumor samples from twenty-nine NSCLC patients who received neoadjuvant
immunotherapy with
sintilimab, an anti-PD-1 drug, were subjected to targeted
DNA sequencing and PD-L1 immunochemistry staining. The pathological response was positively correlated with
tumor proportion score (TPS) of PD-L1 and negatively correlated with copy number gain (CNgain) burden. Of note, the combination of CNgain burden and TPS can better stratify major pathological response (MPR) patients than did CNgain or TPS alone. Whereas, TMB showed a limited correlation with pathological regression. Additionally, PD-1 blockade led to an increase in CD8+PD-1-T cells which was clinically relevant to MPR as evaluated by multiplex immunofluorescence. A significant reduction in CD19+ cells was observed in the Non-MPR group but not in the MPR group, indicating the involvement of B cells in improving neoadjuvant
immunotherapy response in NSCLC. Together, our study provides new data for the correlation of PD-L1 expression and genomic factors with drug response in neoadjuvant
immunotherapy settings in NSCLC. The changes of TIME may provide novel insight into the immune responses to neoadjuvant anti-PD-1
therapy.