title: PD-1 and PD-L1 Expression in NSCLC Indicate a Favorable Prognosis in Defined Subgroups.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Muenster, 48149 Muenster, Germany.
authors: Lars Henning
authors: LH
authors: Schmidt
authors: Pulmonary Division, Department of Medicine III, Johannes Gutenberg University Medical Center, 55101 Mainz, Germany.
authors: Andreas
authors: A
authors: Kümmel
authors: Institute of Biostatistics and Clinical Research, University of Münster, Münster, Germany.
authors: Dennis
authors: D
authors: Görlich
authors: Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Muenster, 48149 Muenster, Germany.
authors: Michael
authors: M
authors: Mohr
authors: Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Muenster, 48149 Muenster, Germany.
authors: Sebastian
authors: S
authors: Bröckling
authors: Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Muenster, 48149 Muenster, Germany.
authors: Jan Henrik
authors: JH
authors: Mikesch
authors: Gerhard-Domagk-Institute of Pathology, University of Münster, Münster, Germany.
authors: Inga
authors: I
authors: Grünewald
authors: Chest Surgery, Klinikum Bremen Ost, 28325 Bremen, Bremen, Germany.
authors: Alessandro
authors: A
authors: Marra
authors: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, United States of America.
authors: Anne M
authors: AM
authors: Schultheis
authors: Gerhard-Domagk-Institute of Pathology, University of Münster, Münster, Germany.
authors: Eva
authors: E
authors: Wardelmann
authors: Department of Medicine IV, Hematology and Oncology, University of Halle, 06120 Halle, Germany.
authors: Carsten
authors: C
authors: Müller-Tidow
authors: Institute for Pathology at St. Franziskus-Hospital, Münster, 48145 Münster, Germany.
authors: Tilmann
authors: T
authors: Spieker
authors: Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Muenster, 48149 Muenster, Germany.
authors: Christoph
authors: C
authors: Schliemann
authors: Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Muenster, 48149 Muenster, Germany.
authors: Wolfgang E
authors: WE
authors: Berdel
authors: Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Muenster, 48149 Muenster, Germany.
authors: Rainer
authors: R
authors: Wiewrodt
authors: Gerhard-Domagk-Institute of Pathology, University of Münster, Münster, Germany.
authors: Wolfgang
authors: W
authors: Hartmann
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D000368:Aged; D060890:B7-H1 Antigen / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D018287:Carcinoma, Large Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor