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PD-1 and PD-L1 Expression in NSCLC Indicate a Favorable Prognosis in Defined Subgroups

Background: Immunotherapy can become a crucial therapeutic option to improve prognosis for lung cancer patients. First clinical trials with therapies targeting the programmed cell death receptor PD-1 and its ligand PD-L1 have shown promising results in several solid tumors. However, in lung cancer the diagnostic, prognostic and predictive value of these immunologic factors remains unclear. Method: The impact of both factors was evaluated in a study collective of 321 clinically well-annotated patients with non-small lung cancer (NSCLC) using immunohistochemistry. Results: PD-1 expression by tumor infiltrating lymphocytes (TILs) was found in 22%, whereas tumor cell associated PD-L1 expression was observed in 24% of the NSCLC tumors. In Fisher’s exact test a positive correlation was found for PD-L1 and Bcl-xl protein expression (p = 0.013). Interestingly, PD-L1 expression on tumor cells was associated with improved overall survival in pulmonary squamous cell carcinomas (SCC, p = 0.042, log rank test), with adjuvant therapy (p = 0.017), with increased tumor size (pT2-4, p = 0.039) and with positive lymph node status (pN1-3, p = 0.010). These observations were confirmed by multivariate cox regression models. Conclusion: One major finding of our study is the identification of a prognostic implication of PD-L1 in subsets of NSCLC patients with pulmonary SCC, with increased tumor size, with a positive lymph node status and NSCLC patients who received adjuvant therapies. This study provides first data for immune-context related risk stratification of NSCLC patients. Further studies are necessary both to confirm this observation and to evaluate the predictive value of PD-1 and PD-L1 in NSCLC in the context of PD-1 inhibition.

Titel: PD-1 and PD-L1 Expression in NSCLC Indicate a Favorable Prognosis in Defined Subgroups
Verfasser: Schmidt, Lars Henning GND
Kümmel, Andreas GND
Görlich, Dennis
Mohr, Michael
Bröckling, Sebastian GND
Mikesch, Jan-Henrik GND
Grünewald, Inga
Marra, Alessandro
Schultheis, Anne Maria GND
Müller-Tidow, Carsten GND
Spieker, Tilmann
Schliemann, Christoph GND
Berdel, Wolfgang E. GND
Wiewrodt, Rainer Gerhard GND
Hartmann, Wolfgang
Organisation: FB 05: Medizinische Fakultät
Dokumenttyp: Artikel
Medientyp: Text
Erscheinungsdatum: 27.08.2015
Publikation in MIAMI: 04.12.2015
Datum der letzten Änderung: 16.09.2016
Quelle: PLoS ONE 10 (2015) 8, e0136023, 1-15
Fachgebiete: Medizin und Gesundheit
Lizenz: CC BY 4.0
Sprache: Englisch
Anmerkungen: Finanziert durch den Open-Access-Publikationsfonds 2015/2016 der Westfälischen Wilhelms-Universität Münster (WWU Münster).
Format: PDF-Dokument
URN: urn:nbn:de:hbz:6-07269496604
DOI: 10.1371/journal.pone.0136023
ISSN: 1932-6203