Monitoring PD-L1 Expression on Circulating Tumor–Associated Cells in Recurrent Metastatic Non–Small-Cell Lung Carcinoma Predicts Response to Immunotherapy With Radiation Therapy

Jillian A. Moran, Daniel L. Adams, Martin J. Edelman, Pablo Lopez, Jianzhong He, Yawei Qiao, Ting Xu, Zhongxing Liao, Kirby P. Gardner, Cha-Mei Tang, Steven H. Lin

Research output: Contribution to journalArticlepeer-review

Abstract

PURPOSE: Current diagnostic methods to determine programmed death 1 (PD-1) receptor and its ligand (PD-L1)/PD-1 immunotherapy (immune checkpoint inhibitor [ICI]) efficacy in recurrent or metastatic non-small-cell lung carcinoma (rmNSCLC) are imprecise. Although previously shown that patients with high tumor PD-L1 (≥ 50%) demonstrate clinical benefit in the form of disease reduction and improved survival, patients with low PD-L1 (< 50%) sometimes benefit from treatment. Since the PD-L1/PD-1 pathway is dynamic, monitoring PD-L1 levels during treatment may be more accurate than a static baseline tumor biopsy; however, rebiopsying the primary or metastatic disease is rarely feasible. Liquid biopsies that measure the upregulation of PD-L1 on tumor-associated cells (TACs), ie, cancer-associated macrophage-like cells and circulating tumor cells, have been performed, but their predictive value for ICI therapy efficacy is unknown.

MATERIALS AND METHODS: We initiated a single-blind prospective study to evaluate TAC PD-L1 expression changes in rmNSCLC from blood samples before (T0) and after (T1) treatment with ICI (ICI, n = 41) or without ICI (no ICI, n = 41). Anonymized blood was filtered to isolate TACs, which were then quantified for high/low PD-L1 expression. Progression-free survival (PFS) or overall survival (OS) hazard ratios (HRs) were evaluated at 18 and 24 months by censored univariate analysis.

RESULTS: Increased TAC PD-L1 expression between T0 and T1 in patients who were not treated with ICI had no relationship with PFS or OS. However, increased TAC PD-L1 expression between T0 and T1 in patients treated with ICI had significantly better PFS (HR, 3.49; 95% CI, 1.5 to 8.3; P = .0091) and OS (HR, 3.058; 95% CI, 1.2 to 7.9; P = .0410).

CONCLUSION: Blood-based monitoring of dynamic changes in PD-L1 in TACs appears to identify patients with rmNSCLC who may benefit from ICI.

Original languageAmerican English
Article numbere2200457
Pages (from-to)e2200457
JournalJCO Precision Oncology
Volume6
DOIs
StatePublished - Dec 2022

Keywords

  • Antineoplastic Agents, Immunological/therapeutic use
  • B7-H1 Antigen
  • Biomarkers, Tumor/analysis
  • Carcinoma, Non-Small-Cell Lung/therapy
  • Humans
  • Immunotherapy/methods
  • Lung Neoplasms/therapy
  • Neoplasm Recurrence, Local/chemically induced
  • Neoplastic Cells, Circulating
  • Programmed Cell Death 1 Receptor
  • Prospective Studies
  • Single-Blind Method

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