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Cancer Epidemiol Biomarkers Prev. 2017 Jul;26(7):1139-1145. doi: 10.1158/1055-9965.EPI-17-0120. Epub 2017 Apr 26.

Cellular Expression of PD-L1 in the Peripheral Blood of Lung Cancer Patients is Associated with Worse Survival.

Author information

1
Section of Thoracic Surgery, Department of Surgery, Yale School of Medicine, New Haven, Connecticut. Daniel.boffa@yale.edu.
2
Epic Sciences, San Diego, California.
3
Section of Thoracic Surgery, Department of Surgery, Yale School of Medicine, New Haven, Connecticut.
4
Cancer Outcomes, Public Policy, and Effectiveness Research Center, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut.
5
Department of Medicine, University of California San Diego, La Jolla, California.
6
University of Southern California, Norris Cancer Center, Los Angeles, California.

Abstract

Background: Lung cancer treatment has become increasingly dependent upon invasive biopsies to profile tumors for personalized therapy. Recently, tumor expression of programmed death-ligand 1 (PD-L1) has gained interest as a potential predictor of response to immunotherapy. Circulating biomarkers present an opportunity for tumor profiling without the risks of invasive procedures. We characterized PD-L1 expression within populations of nucleated cells in the peripheral blood of lung cancer patients in hopes of expanding the role of liquid biopsy in this setting.Methods: Peripheral blood samples from a multi-institutional prospective study of patients with clinical diagnosis of lung cancer were subjected to cytomorphometric and immunohistochemical evaluation using single-cell, automated slide-based, digital pathology. PD-L1 expression was determined by immunofluorescence.Results: PD-L1 expression was detected within peripheral circulating cells associated with malignancy (CCAM) in 26 of 112 (23%) non-small cell lung cancer patients. Two distinct populations of nucleated, nonhematolymphoid, PD-L1-expressing cells were identified; cytokeratin positive (CK+, PD-L1+, CD45-) and cytokeratin negative (CK-, PD-L1+, CD45-) cells, both with cytomorphometric features (size, nuclear-to-cytoplasm ratio) consistent with tumor cells. Patients with >1.1 PD-L1(+) cell/mL (n = 14/112) experienced worse overall survival than patients with ≤1.1 PD-L1(+) cell/mL (2-year OS: 31.2% vs. 78.8%, P = 0.00159). In a Cox model adjusting for stage, high PD-L1(+) cell burden remained a significant predictor of mortality (HR = 3.85; 95% confidence interval, 1.64-9.09; P = 0.002).Conclusions: PD-L1 expression is detectable in two distinct cell populations in the peripheral blood of lung cancer patients and is associated with worse survival.Impact: These findings could represent a step forward in the development of minimally invasive liquid biopsies for the profiling of tumors. Cancer Epidemiol Biomarkers Prev; 26(7); 1139-45. ©2017 AACR.

PMID:
28446544
PMCID:
PMC5500408
DOI:
10.1158/1055-9965.EPI-17-0120
[Indexed for MEDLINE]
Free PMC Article

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