PD-1 and PD-L1 Expression in NSCLC Indicate a Favorable Prognosis in Defined Subgroups.
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 diagnosti...
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doaj-f6ac7ba149844067990502ff5a29b1462020-11-25T02:12:57ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01108e013602310.1371/journal.pone.0136023PD-1 and PD-L1 Expression in NSCLC Indicate a Favorable Prognosis in Defined Subgroups.Lars Henning SchmidtAndreas KümmelDennis GörlichMichael MohrSebastian BröcklingJan Henrik MikeschInga GrünewaldAlessandro MarraAnne M SchultheisEva WardelmannCarsten Müller-TidowTilmann SpiekerChristoph SchliemannWolfgang E BerdelRainer WiewrodtWolfgang HartmannImmunotherapy 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.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.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.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.http://europepmc.org/articles/PMC4552388?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lars Henning Schmidt Andreas Kümmel Dennis Görlich Michael Mohr Sebastian Bröckling Jan Henrik Mikesch Inga Grünewald Alessandro Marra Anne M Schultheis Eva Wardelmann Carsten Müller-Tidow Tilmann Spieker Christoph Schliemann Wolfgang E Berdel Rainer Wiewrodt Wolfgang Hartmann |
spellingShingle |
Lars Henning Schmidt Andreas Kümmel Dennis Görlich Michael Mohr Sebastian Bröckling Jan Henrik Mikesch Inga Grünewald Alessandro Marra Anne M Schultheis Eva Wardelmann Carsten Müller-Tidow Tilmann Spieker Christoph Schliemann Wolfgang E Berdel Rainer Wiewrodt Wolfgang Hartmann PD-1 and PD-L1 Expression in NSCLC Indicate a Favorable Prognosis in Defined Subgroups. PLoS ONE |
author_facet |
Lars Henning Schmidt Andreas Kümmel Dennis Görlich Michael Mohr Sebastian Bröckling Jan Henrik Mikesch Inga Grünewald Alessandro Marra Anne M Schultheis Eva Wardelmann Carsten Müller-Tidow Tilmann Spieker Christoph Schliemann Wolfgang E Berdel Rainer Wiewrodt Wolfgang Hartmann |
author_sort |
Lars Henning Schmidt |
title |
PD-1 and PD-L1 Expression in NSCLC Indicate a Favorable Prognosis in Defined Subgroups. |
title_short |
PD-1 and PD-L1 Expression in NSCLC Indicate a Favorable Prognosis in Defined Subgroups. |
title_full |
PD-1 and PD-L1 Expression in NSCLC Indicate a Favorable Prognosis in Defined Subgroups. |
title_fullStr |
PD-1 and PD-L1 Expression in NSCLC Indicate a Favorable Prognosis in Defined Subgroups. |
title_full_unstemmed |
PD-1 and PD-L1 Expression in NSCLC Indicate a Favorable Prognosis in Defined Subgroups. |
title_sort |
pd-1 and pd-l1 expression in nsclc indicate a favorable prognosis in defined subgroups. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2015-01-01 |
description |
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.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.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.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. |
url |
http://europepmc.org/articles/PMC4552388?pdf=render |
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