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The integration of systemic and tumor PD-L1 as a predictive biomarker of clinical outcomes in patients with advanced NSCLC treated with PD-(L)1blockade agents

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Abstract

Background

Tumor PD-L1 expression is a predictive biomarker for patients with NSCLC receiving PD-(L)1 blockade agents. However, although increased tumor PD-L1 expression predicts responsiveness, clinical benefit has been observed regardless of tumor PD-L1 expression, suggesting the existence of other PD-L1 sources. The aim of our study was to analyze whether integrating systemic and tumor PD-L1 is more predictive of efficacy in patients with advanced NSCLC receiving PD-(L)1 blockade agents.

Material and methods

Twenty-nine healthy donors and 119 consecutive patients with advanced NSCLC treated with PD-(L)1 drug were prospectively included. Pretreatment blood samples were collected to evaluate PD-L1 levels on circulating immune cells, platelets (PLTs), platelet microparticles (PMPs), and the plasma soluble PD-L1 concentration (sPD-L1). Tumor PD-L1 status was assessed by immunohistochemistry. The percentages of circulating PD-L1 + leukocytes, sPD-L1 levels, and tumor PD-L1 were correlated with efficacy.

Results

No differences in the percentages of circulating PD-L1 + leukocytes were observed according to tumor PD-L1 expression. Significantly longer progression-free survival was observed in patients with higher percentages of PD-L1 + CD14 + , PD-L1 + neutrophils, PD-L1 + PLTs, and PD-L1 + PMPs and significantly longer overall survival was observed in patients with higher percentages of PD-L1 + CD14 + and high tumor PD-L1 expression. Integrating the PD-L1 data of circulating and tumor PD-L1 results significantly stratified patients according to the efficacy of PD-(L1) blockade agents.

Conclusions

Our results suggest that integrating circulating PD-L1 + leukocytes, PLT, PMPs, and sPD-L1 and tumor PD-L1 expression may be helpful to decide on the best treatment strategy in patients with advanced NSCLC who are candidates for PD-(L)1 blockade agents.

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Abbreviations

CH:

Chemotherapy

CI:

Confidence interval

ECOG PS:

Eastern Cooperative Oncology Group performance status

FITC:

Fluorescein

HD:

Healthy donors

HR:

Hazard Ratio

IO:

Immunotherapy

IPD:

Integrated PD-L1 data

irAEs:

Immune-related adverse events

IHC:

Immunohistochemistry

iRECIST:

Immune-Response Evaluation Criteria In Solid Tumors

NSCLC:

Non-small cell lung cancer

PD-1:

Programmed death-1

PD-L1:

Programmed death-ligand 1

PLTs:

Platelets

PMPs:

Platelet microparticles

sPD-L1:

Plasma concentrations of soluble PD-L1

OS:

Overall survival

PFS:

Progression-free-survival

TPS:

Tumor proportion score

RECIST:

Response Evaluation Criteria in Solid Tumors

NE:

Not evaluable

PE:

Phycoerythrin

PECy7:

Phycoerythrin Cyanine 7

PECy5:

Phycoerythrin Cyanine 5

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Acknowledgments

SV was supported by “Fondo Investigaciones Sanitarias” and a participant in the Program for the Stabilization of Investigators from the “Direcció i d’Estrategia I Coordinació del Departament Salut de la Generalitat de Catalunya.”

Funding

This work was supported by the Bristol Myers Squibb.

Author information

Author notes

  1. Carlos Zamora Atenza and Geòrgia Anguera have contributed equally to this work. Sílvia Vidal and Margarita Majem Tarruella have contributed equally to this work.

Authors and Affiliations

  1. Group of Immunology-Inflammatory Diseases, Biomedical Research Institut Sant Pau (IIB Sant Pau), Barcelona, Spain

    Carlos Zamora Atenza, M. Angels Ortiz, Maria Mulet & Sílvia Vidal

  2. Department of Medical Oncology, Hospital de La Santa Creu I San Pau. C, Sant Antoni Maria Claret 167 08025, Barcelona, Spain

    Geòrgia Anguera, Mariona Riudavets Melià, Ivana Sullivan, Andrés Barba Joaquin, Jorgina Serra Lopez & Margarita Majem

  3. Department of Medicine, Universitat Autónoma de Barcelona (UAB), Barcelona, Spain

    Geòrgia Anguera

  4. Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France

    Mariona Riudavets Melià

  5. Department of Immunology, Hospital de La Santa Creu I Sant Pau, Barcelona, Spain

    Letícia Alserawan De Lamo

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  1. Carlos Zamora Atenza
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Contributions

All authors were involved in revising intellectual content, and all authors approved the final version for publication. CZ, MM, LA, and MAO performed cellular staining and flow cytometry analysis and ELISAs. CZ and MM and MAO analyzed results of flow cytometry and ELISAS; GA, MR, IS, AB, JS, OG, JG, and MM collected samples and clinical data; CZ and SV performed statistical analysis.GA, CZ, MM and SV wrote the manuscript. MM, and SV designed the study.

Corresponding author

Correspondence to Margarita Majem.

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The authors declare that they have no conflict of interest.

Ethical approval

The study was conducted in accordance with the Helsinki Declaration and approved by the Research Ethics Board of Hospital de la Santa Creu I Sant Pau, Barcelona (IIBSP-PDL-2017–82).

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Zamora Atenza, C., Anguera, G., Riudavets Melià, M. et al. The integration of systemic and tumor PD-L1 as a predictive biomarker of clinical outcomes in patients with advanced NSCLC treated with PD-(L)1blockade agents. Cancer Immunol Immunother 71, 1823–1835 (2022). https://doi.org/10.1007/s00262-021-03107-y

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