Biomarker, Exhaustion, Ki-67, Memory T cells, Immune checkpoint inhibitor, PD-1/PD-L1 signaling, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

Abstract Aims Developing predictive biomarkers for immune checkpoint inhibitors (ICIs) is important. Programmed cell death protein-1 (PD-1) receptor occupancy by anti-PD-1 antibodies on circulating T cells varies among patients. However, the association between the exhaustion of these antibody-bound T cells and the clinical efficacy of ICIs remains unknown. Therefore, the present study was aimed at evaluating this association. Methods This prospective cohort study included patients with advanced non-small cell lung cancer (NSCLC) and esophageal squamous cell carcinoma (ESCC) who received pembrolizumab therapy. Peripheral blood samples were collected during the second cycle of chemotherapy. We analyzed the relationship between exhaustion markers in pembrolizumab-bound (PB) T cells and clinical response. Results A total of 21 patients were analyzed, including 12 patients with NSCLC and 9 patients with ESCC. The expression of Ki-67 in PB-CD8+ TCM and TEM was negatively correlated with both clinical response and overall survival. Conclusion The expression of Ki-67 of PB-CD8+ TCM and TEM can serve as a predictive biomarker for the clinical benefit of pembrolizumab therapy. Our study suggests that analyzing antibody-bound T cells could be a novel approach to predict the clinical outcomes of PD-1 blockade therapy.