Abstract

PD-L1 expression is the most useful predictive biomarker for immunotherapy efficacy on non-small cell lung cancer (NSCLC), and CD8+ tumor-infiltrating lymphocytes (CD8+ TILs) play an essential role in the clinical activity of immunotherapy. PD-L1 is found on the exosome’s surface, and PD-L1 expressing exosomes can inhibit antitumor immune responses. This study aimed to analyze tumor PD-L1 expression, serum exosomal PD-L1, and CD8+ TILs to investigate anti-PD-1 response and clinicopathological outcomes in NSCLC. One hundred twenty patients with stage I–III NSCLC were enrolled, and serum samples collected during the initial surgery were pooled. The Human CD274/PD-L1 ELISA kit was used to quantify the exosomal PD-L1. Exosomal PD-L1 levels were significantly correlated with tumor PD-L1 levels (p < 0.001) and the number of CD8+ TILs (p = 0.001). Patients with exosomal PD-L1 ≥ 166 pg/mL tended to have a worse RFS than those with < 166 pg/mL in all stage (p = 0.163) and stage I patients (p = 0.116). Seventeen patients exhibited postoperative recurrences and received anti-PD-1 treatment. The disease control rate of patients with exosomal PD-L1 ≥ 166 pg/mL was 100%. The measurement of serum exosomal PD-L1 as a quantitative factor with tumor PD-L1 status may help predict anti-PD-1 response and clinical outcomes in patients with NSCLC.

Highlights

  • programmed cell death ligand 1 (PD-L1) expression is the most useful predictive biomarker for immunotherapy efficacy on non-small cell lung cancer (NSCLC), and CD8+ tumor-infiltrating lymphocytes (CD8+ TILs) play an essential role in the clinical activity of immunotherapy

  • Serum PD-L1 levels significantly correlated with tumor PD-L1 level (R = 0.32, p < 0.001; Fig. 2A) and the number of CD8+ TILs (R = 0.29, p = 0.001; Fig. 2B); tumor PD-L1 levels were associated with the number of CD8+ TILs (R = 0.32, p < 0.001; Fig. 2C)

  • In all patients with wild type epidermal growth factor receptor (EGFR) tumors, serum PD-L1 levels correlated with tumor PD-L1 level (R = 0.35, p = 0.004; Fig. 2D) and the number of CD8+ TILs (R = 0.26, p = 0.034; Fig. 2E), while tumor PD-L1 levels tended to be correlated with the number of CD8+ TILs (R = 0.21, p = 0.083; Fig. 2F)

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Summary

Introduction

PD-L1 expression is the most useful predictive biomarker for immunotherapy efficacy on non-small cell lung cancer (NSCLC), and CD8+ tumor-infiltrating lymphocytes (CD8+ TILs) play an essential role in the clinical activity of immunotherapy. This study aimed to analyze tumor PD-L1 expression, serum exosomal PD-L1, and CD8+ TILs to investigate anti-PD-1 response and clinicopathological outcomes in NSCLC. The measurement of serum exosomal PD-L1 as a quantitative factor with tumor PD-L1 status may help predict anti-PD-1 response and clinical outcomes in patients with NSCLC. Abbreviations NSCLC Non-small cell lung caner PD-1 Programmed cell death-1 PD-L1 Programmed cell death ligand 1 CD8+ TIL CD8+ tumor-infiltrating lymphocyte ICI Immune checkpoint inhibitor IHC Immunohistochemical ELISA Enzyme-linked immuno-sorbent assay EGFR Epidermal growth factor receptor ALK Anaplastic lymphoma kinase TMB Tumor mutation burden RFS Recurrence-free survival CT Computed tomography PR Partial response SD Stable disease PD Progressive disease. The clinical impact of exosomal PD-L1 and CD8+ TILs on the anti-PD-1/PD-L1 response and on survival in early-stage NSCLC remains unclear

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