CD57+CD8+ T cells and response to PD-1/PD-L1 blockade in patients with NSCLC.

e21189 Background: Immune checkpoint inhibitors (ICIs) are currently widely used and have made significant advances in the treatment of patients with advanced non-small cell lung cancer (NSCLC). Despite available biomarker stratification, clinical responses vary. Thus, potential biomarkers for identifying patients who will benefit from the immunotherapy are urgently needed. Methods: We applied mass cytometry (CyTOF) to deeply analyze the association of cell subpopulations in PBMC before and after single-agent immunotherapy with clinical outcomes in advanced NSCLC. We then performed flow cytometry of peripheral blood and multiplex immunohistochemistry/immunofluorescence (mIHC/IF) of tumor samples to validate our conclusion. In addition, RNA sequencing (RNA-seq) was performed to explore the mechanism of the ICIs treatment efficacy of NSCLC. Results: In a prospective cohort (n = 20), high CD57+ CD8+ T cell proportion in PBMC detected by CyTOF was associated with good response ( p= 0.014) in advanced NSCLC patients. The result was confirmed in an independent, prospective cohort (n = 30) using flow cytometry, and the specificity and sensitivity of flow cytometry was then assessed in this cohort. CD57+CD8+ T cell proportion, as determined by flow cytometry, successfully stratified responders and non-responders to ICIs ( P< 0.001). We also confirmed this result in FFPE samples (n = 31) ( p= 0.004). In addition, transcriptomic differences between CD57+CD8+ T cells and CD57-CD8+ T cells were found performed by RNA sequencing (RNA-seq). Conclusions: Our results suggest that CD57+CD8+ T cell proportion may serve as a predictive value of response to PD-1/PD-L1 checkpoint blockade. Further validation in additional NSCLC cohorts is warranted.