Chemotherapy treatment is associated with altered PD-L1 expression in lung cancer patients
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.
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.
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.
KeywordsPD-L1 PD-1 Immunohistochemistry Lung cancer Chemotherapy
Non-small cell lung cancer
Programmed cell death ligand-1
Programmed cell death-1
Squamous cell carcinoma
Small cell lung cancer
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.
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.
Compliance with ethical standards
Conflict of interest
The authors declare no conflict of interest.
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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