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Peer-reviewedCC BY-NC 4.0ImmunoTargets and Therapy

Early Assessment of Circulating Tumor Cells and Their PD-L1 Expression as Predictive Biomarkers in Metastatic Non-Small Cell Lung Cancer Patients Treated with Immunotherapy: An Exploratory Study

1 more authors
15 affiliations
  1. 1Acute Respiratory Disease and Thoracic Oncology Department, Hospices Civils de Lyon, Oullins-Pierre-Benite, France
  2. 2Claude Bernard University Lyon I, Villeurbanne, France
  3. 3Center for Innovation in Cancerology of Lyon (CICLY) EA 3738, Faculty of Medicine and Maieutic Lyon Sud, Oullins-Pierre-Benite, France
  4. 4Institute of Pharmaceutical and Biological Sciences (ISPB), Claude Bernard University Lyon I, Villeurbanne, France
  5. 5Department of Biochemistry and Molecular Biology, Hospices Civils de Lyon, Oullins-Pierre-Benite, France
  6. 6Pharmacology and Toxicology platform, Department of Biochemistry and Molecular Biology, Hospices Civils de Lyon, Lyon, France
  7. 7Clinical Research Platform, Hospices Civils de Lyon - Cancer Institute (IC-HCL), Lyon, France
  8. 8Early Phase Studies in Oncology Unit (EPSILYON), Hospices Civils de Lyon - Cancer Institute (IC-HCL), Lyon, France
  9. 9Medical Biology Multisite Laboratory (LBMMS), Department of Molecular Biology and Biochemistry, Hospices Civils de Lyon, Lyon, France
  10. 10Pathology Department, Hospices Civils de Lyon, Bron, France
  11. 11Promise Proteomics, Grenoble, France
  12. 12Head and Neck Surgery Department, Hospices Civils de Lyon, Lyon, France
  13. 13Cellular and Molecular Radiobiology- UMR CNRS 5822/IP2I, Faculty of Medicine and Maieutic Lyon Sud, Oullins-Pierre-Benite, France
  14. 14Department of Pharmacology-Physiology-Toxicology, Institute of Pharmaceutical and Biological Sciences of Lyon, Claude Bernard University Lyon I, Villeurbanne, France
  15. 15RESHAPE Unit (Research on Healthcare Performance), INSERM U1290, Claude Bernard University Lyon I, Villeurbanne, France

Abstract

Introduction: The prognosis of metastatic non-small cell lung cancer (mNSCLC) has improved in recent years but therapeutic benefit remains heterogeneous, underscoring the need for reliable biomarkers. Liquid biopsy techniques, including the analysis of circulating tumor cells (CTCs) and Programmed death-ligand 1 (PD-L1) expression on CTCs (PD-L1-CTCs), have emerged as promising tools.

Materials and Methods: We conducted a retrospective study in a cohort of mNSCLC patients treated with Immune Checkpoint Inhibitors (ICIs) to evaluate the predictive value of these biomarkers at baseline and at an early time point during treatment. CTCs were captured with the ClearCell® FX platform and then assessed for PD-L1 by immunostaining. Therapeutic drug monitoring of nivolumab and pembrolizumab was performed.

Results: Thirty-seven mNSCLC patients were enrolled. The median CTCs count was 35 CTCs per 7.5 mL of whole blood (standard deviation ± 939). PD-L1-CTCs were detected in 51% of patients. No correlation was found between PD-L1-CTCs and PD-L1 on tumor Formalin-Fixed, Paraffin-Embedded (FFPE) tissue. Higher-than-median CTCs count was associated with a trend toward worse outcomes. In contrast, PD-L1 expression on CTCs did not predict treatment response. Most patients presented a trough concentration of ICI at cure 3 above 10 µg/mL, regardless clinical response.

Conclusion: Baseline CTCs levels tended to be associated with clinical outcomes, whereas PD-L1 expression on CTCs was not. Early evaluation of changes in these two parameters did not improve outcome prediction under ICI treatment. Larger studies with longer follow-up and more in-depth analyses are warranted to further define the prognostic and predictive value of CTC-based biomarkers.

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BibTeX
@article{grolleau2026early,
  title = {{Early Assessment of Circulating Tumor Cells and Their PD-L1 Expression as Predictive Biomarkers in Metastatic Non-Small Cell Lung Cancer Patients Treated with Immunotherapy: An Exploratory Study}},
  author = {Emmanuel Grolleau and David Barthelemy and Aurélien Millet and Sara Calattini and Gaelle Lescuyer and Agathe Komaroff and Nazim Benzerdjeb and Dorothée Lebert and Pierre Philouze and Marie Piecyk and Jerome Guitton and Sébastien Couraud and Léa Payen},
  journal = {ImmunoTargets and Therapy},
  year = {2026},
  month = oct,
  doi = {10.2147/itt.s614110},
  url = {https://doi.org/10.2147/itt.s614110},
  note = {CC BY-NC 4.0},
}
RIS
TY  - JOUR
TI  - Early Assessment of Circulating Tumor Cells and Their PD-L1 Expression as Predictive Biomarkers in Metastatic Non-Small Cell Lung Cancer Patients Treated with Immunotherapy: An Exploratory Study
AU  - Emmanuel Grolleau
AU  - David Barthelemy
AU  - Aurélien Millet
AU  - Sara Calattini
AU  - Gaelle Lescuyer
AU  - Agathe Komaroff
AU  - Nazim Benzerdjeb
AU  - Dorothée Lebert
AU  - Pierre Philouze
AU  - Marie Piecyk
AU  - Jerome Guitton
AU  - Sébastien Couraud
AU  - Léa Payen
PY  - 2026
DA  - 2026/10/27
JO  - ImmunoTargets and Therapy
DO  - 10.2147/itt.s614110
UR  - https://doi.org/10.2147/itt.s614110
AB  - Introduction: The prognosis of metastatic non-small cell lung cancer (mNSCLC) has improved in recent years but therapeutic benefit remains heterogeneous, underscoring the need for reliable biomarkers. Liquid biopsy techniques, including the analysis of circulating tumor cells (CTCs) and Programmed death-ligand 1 (PD-L1) expression on CTCs (PD-L1-CTCs), have emerged as promising tools.  Materials and Methods: We conducted a retrospective study in a cohort of mNSCLC patients treated with Immune Checkpoint Inhibitors (ICIs) to evaluate the predictive value of these biomarkers at baseline and at an early time point during treatment. CTCs were captured with the ClearCell® FX platform and then assessed for PD-L1 by immunostaining. Therapeutic drug monitoring of nivolumab and pembrolizumab was performed.  Results: Thirty-seven mNSCLC patients were enrolled. The median CTCs count was 35 CTCs per 7.5 mL of whole blood (standard deviation ± 939). PD-L1-CTCs were detected in 51% of patients. No correlation was found between PD-L1-CTCs and PD-L1 on tumor Formalin-Fixed, Paraffin-Embedded (FFPE) tissue. Higher-than-median CTCs count was associated with a trend toward worse outcomes. In contrast, PD-L1 expression on CTCs did not predict treatment response. Most patients presented a trough concentration of ICI at cure 3 above 10 µg/mL, regardless clinical response.  Conclusion: Baseline CTCs levels tended to be associated with clinical outcomes, whereas PD-L1 expression on CTCs was not. Early evaluation of changes in these two parameters did not improve outcome prediction under ICI treatment. Larger studies with longer follow-up and more in-depth analyses are warranted to further define the prognostic and predictive value of CTC-based biomarkers.
SN  - 2253-1556
ER  -