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Chemotherapy treatment is associated with altered PD-L1 expression in lung cancer patients

  • Original Article – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Objectives

While the predictive value of programmed cell death ligand-1 (PD-L1) protein expression for immune checkpoint inhibitor therapy of lung cancer has been extensively studied, the impact of standard platinum-based chemotherapy on PD-L1 or programmed cell death-1 (PD-1) expression is unknown. The aim of this study was to determine the changes in PD-L1 expression of tumor cells (TC) and immune cells (IC), in PD-1 expression of IC, and in the amount of stromal mononuclear cell infiltration after platinum-based chemotherapy in patients with lung cancer.

Materials and methods

We determined the amount of stromal mononuclear cells and PD-L1/PD-1 expressions by immunohistochemistry in bronchoscopic biopsy samples including 20 adenocarcinomas (ADC), 15 squamous cell carcinomas (SCC), 2 other types of non-small cell lung cancer, and 4 small cell lung cancers together with their corresponding surgical resection tissues after platinum-based chemotherapy.

Results

PD-L1 expression of TC decreased in ten patients (24.4%) and increased in three patients (7.32%) after neoadjuvant chemotherapy (p = 0.051). The decrease in PD-L1 expression, however, was significant only in patients who received cisplatin–gemcitabine combination (p = 0.020), while in the carboplatin–paclitaxel group, no similar tendency could be observed (p = 0.432). There was no difference between ADC and SCC groups. Neither PD-1 expression nor the amount of stromal IC infiltration showed significant changes after chemotherapy.

Conclusions

This is the first study, in which both PD-L1 and PD-1 expression were analyzed together with the amount of stromal IC infiltration in different histological subtypes of lung cancer before and after platinum-based chemotherapy. Our results confirm that chemotherapy decreases PD-L1 expression of TC in a subset of patients, therefore, rebiopsy and re-evaluation of PD-L1 expression may be necessary for the indication of immune checkpoint inhibitor therapy.

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Abbreviations

ADC:

Adenocarcinoma

ADSQ:

Adenosquamous carcinoma

IC:

Immune cells

IHC:

Immunohistochemistry

MEC:

Mucoepidermoid carcinoma

NSCLC:

Non-small cell lung cancer

PD-L1:

Programmed cell death ligand-1

PD-1:

Programmed cell death-1

SCC:

Squamous cell carcinoma

SCLC:

Small cell lung cancer

TC:

Tumor cells

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Acknowledgements

We thank Zsuzsanna Kaminszky, Anna Tamási and Mónika Szilágyiné Paulusz for their excellent technical assistance, and Ildikó Krencz for constructing the tissue microarray (TMA) blocks.

Funding

This work was supported by the Research and Technology Innovation Fund (KTIA_NAP_13-2014-0021 to L.R., Z.S., J.M.); Hungarian Science Foundation (OTKA-PD115792 to L.R., OTKA-K116151 to L.R., J.T., B.D., OTKA-K112371 to J.T.); Breast Cancer Research Foundation and the Novo Nordisk Foundation Interdisciplinary Synergy Programme Grant (NNF15OC0016584 to Z.S.). For the remaining authors none were declared.

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Authors and Affiliations

  1. VI. Department of Pulmonology, National Korányi Institute of Pulmonology, Pihenő u. 1, Budapest, 1121, Hungary

    Lívia Rojkó & Judit Moldvay

  2. 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, Budapest, 1085, Hungary

    Lilla Reiniger & Vanda Téglási

  3. MTA-SE NAP, Brain Metastasis Research Group, 2nd Department of Pathology, Hungarian Academy of Sciences, Semmelweis University, Üllői út 93, Budapest, 1091, Hungary

    Lilla Reiniger, Zoltán Szállási & Judit Moldvay

  4. Department of Pulmonology, Semmelweis University, Diósárok u. 1/C, Budapest, 1125, Hungary

    Katalin Fábián

  5. Department of Pathology, Szent Imre Teaching Hospital, Tétényi út 12-16, Budapest, 1115, Hungary

    Katalin Fábián

  6. Department of Physics of Complex Systems, Eötvös Loránd University, Pázmány Péter sétány 1/A, Budapest, 1117, Hungary

    Orsolya Pipek

  7. Department of Thoracic Surgery, National Korányi Institute of Pulmonology, Pihenő u. 1, Budapest, 1121, Hungary

    Attila Vágvölgyi

  8. Department of Thoracic Surgery, National Institute of Oncology-Semmelweis University, Ráth György u. 7-9, Budapest, 1122, Hungary

    László Agócs

  9. Department of Pathology, National Korányi Institute of Pulmonology, Pihenő u. 1, Budapest, 1121, Hungary

    János Fillinger & Zita Kajdácsi

  10. Department of Pathology, National Institute of Oncology, Ráth György u. 7-9, Budapest, 1122, Hungary

    János Fillinger

  11. 2nd Department of Pathology, Semmelweis University, Üllői út 93, Budapest, 1091, Hungary

    József Tímár

  12. Department of Tumor Biology, National Korányi Institute of Pulmonology-Semmelweis University, Pihenő u. 1, Budapest, 1121, Hungary

    Balázs Döme

  13. Comprehensive Cancer Center, Division of Thoracic Surgery, Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria

    Balázs Döme

  14. Children’s Hospital Informatics Program at the Harvard–Massachusetts Institute of Technology, Division of Health Sciences and Technology, Harvard Medical School, A-111, 25 Shattuck St, Boston, MA, 02115, USA

    Zoltán Szállási

  15. Department of Bio and Health Informatics, Technical University of Denmark, Anker Engelunds Vej 1 Bygning 101A, 2800, Kongens Lyngby, Denmark

    Zoltán Szállási

Authors
  1. Lívia Rojkó
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  2. Lilla Reiniger
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  3. Vanda Téglási
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  6. Attila Vágvölgyi
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  7. László Agócs
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  8. János Fillinger
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  9. Zita Kajdácsi
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  10. József Tímár
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  11. Balázs Döme
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  12. Zoltán Szállási
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  13. Judit Moldvay
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Corresponding author

Correspondence to Judit Moldvay.

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The authors declare no conflict of interest.

Ethical approval

Permissions to use the archived tissue have been obtained from the Regional Ethical Committee (Nos: 510/2013, 86/2015, 241/2016).

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Rojkó, L., Reiniger, L., Téglási, V. et al. Chemotherapy treatment is associated with altered PD-L1 expression in lung cancer patients. J Cancer Res Clin Oncol 144, 1219–1226 (2018). https://doi.org/10.1007/s00432-018-2642-4

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  • DOI: https://doi.org/10.1007/s00432-018-2642-4

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