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Published in: Pathology & Oncology Research 2/2020

01-04-2020 | NSCLC | Original Article

The Relationship Between Tumor-Infiltrating Lymphocytes, PD-L1 Expression, Driver Mutations and Clinical Outcome Parameters in Non-Small Cell Lung Cancer Adenocarcinoma in Patients with a Limited to no Smoking History

Authors: Sacha Mignon, Karen Willard-Gallo, Gert Van den Eynden, Roberto Salgado, Lore Decoster, Koen M. Marien, Johan F. Vansteenkiste, Erik Teugels, Jacques De Grève

Published in: Pathology & Oncology Research | Issue 2/2020

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Abstract

Tumor infiltrating lymphocytes (TIL), programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) expression are important prognostic markers. This study aimed to investigate these markers in lung adenocarcinoma (ADC) biopsies from patients with stage IIIB or IV ADC with little or no smoking history, to investigate their prognostic value and to correlate these results with the presence of driver mutations in the tumors. TIL were retrospectively evaluated on hematoxylin and eosin stained slides from 152 tumor samples. PD-1/PD-L1 expression was retrospectively evaluated with PD-1/PD-L1 immunohistochemistry (IHC) double staining on 74 tumor samples with sufficient residual tissue. PD-L1 expression was analysed on stromal cells of the tumor compartment, the tumor cells and TIL and PD-1 on TIL. Median overall survival (OS) was longer in patients with high stromal TIL infiltration compared to patients with low stromal TIL infiltration (68 weeks vs. 35 weeks respectively; p = 0.003). This was observed most prominently in KRAS mutant tumors (95 weeks vs. 12 weeks; p = 0.003). Only PD-L1 expression on tumor stromal cells influenced OS and indicated a worse prognosis (77 weeks vs 25 weeks; p = 0.013). Stromal TIL counts nor PD-1/PD-L1 expression levels were associated with the presence of driver mutations. The results of the current study reinforce the prognostic role of TIL in lung ADC, which is most prominent in KRAS mutant cancers. The results of the PD-1/PD-L1 analysis suggest that stromal cells can effectively suppress the anti-tumor immune response via the PD-L1 pathway.
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Metadata
Title
The Relationship Between Tumor-Infiltrating Lymphocytes, PD-L1 Expression, Driver Mutations and Clinical Outcome Parameters in Non-Small Cell Lung Cancer Adenocarcinoma in Patients with a Limited to no Smoking History
Authors
Sacha Mignon
Karen Willard-Gallo
Gert Van den Eynden
Roberto Salgado
Lore Decoster
Koen M. Marien
Johan F. Vansteenkiste
Erik Teugels
Jacques De Grève
Publication date
01-04-2020
Publisher
Springer Netherlands
Published in
Pathology & Oncology Research / Issue 2/2020
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI
https://doi.org/10.1007/s12253-019-00670-9

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