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PLoS One. 2015 Aug 27;10(8):e0136023. doi: 10.1371/journal.pone.0136023. eCollection 2015.

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

Author information

1
Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Muenster, 48149 Muenster, Germany.
2
Pulmonary Division, Department of Medicine III, Johannes Gutenberg University Medical Center, 55101 Mainz, Germany.
3
Institute of Biostatistics and Clinical Research, University of Münster, Münster, Germany.
4
Gerhard-Domagk-Institute of Pathology, University of Münster, Münster, Germany.
5
Chest Surgery, Klinikum Bremen Ost, 28325 Bremen, Bremen, Germany.
6
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, United States of America.
7
Department of Medicine IV, Hematology and Oncology, University of Halle, 06120 Halle, Germany.
8
Institute for Pathology at St. Franziskus-Hospital, Münster, 48145 Münster, Germany.

Abstract

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.

PMID:
26313362
PMCID:
PMC4552388
DOI:
10.1371/journal.pone.0136023
[Indexed for MEDLINE]
Free PMC Article

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