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

Authors

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

Publication Date

12-1-2022

Journal

JCO Precision Oncology

DOI

10.1200/PO.22.00457

PMID

36516370

PMCID

PMC10166406

PubMedCentral® Posted Date

12-14-2022

PubMedCentral® Full Text Version

Post-print

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.

Keywords

Humans, Antineoplastic Agents, Immunological, B7-H1 Antigen, Biomarkers, Tumor, Carcinoma, Non-Small-Cell Lung, Immunotherapy, Lung Neoplasms, Neoplasm Recurrence, Local, Neoplastic Cells, Circulating, Programmed Cell Death 1 Receptor, Prospective Studies, Single-Blind Method

Published Open-Access

yes

Recommended Citation

Moran, Jillian A; Adams, Daniel L; Edelman, Martin J; et al., "Monitoring PD-L1 Expression on Circulating Tumor-Associated Cells in Recurrent Metastatic Non-Small-Cell Lung Carcinoma Predicts Response to Immunotherapy With Radiation Therapy" (2022). Faculty, Staff and Student Publications. 4748.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4748