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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adenocarcinoma / therapy
  • Aged
  • B7-H1 Antigen / metabolism*
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Large Cell / metabolism*
  • Carcinoma, Large Cell / mortality
  • Carcinoma, Large Cell / pathology
  • Carcinoma, Large Cell / therapy
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / therapy
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy
  • Combined Modality Therapy
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoenzyme Techniques
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy
  • Male
  • Neoplasm Grading
  • Neoplasm Staging
  • Prognosis
  • Programmed Cell Death 1 Receptor / metabolism*
  • Retrospective Studies
  • Survival Rate

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor

Grant support

NSCLC research in the authors' laboratory is funded by the Innovative Medizinische Forschung Münster University (IMF: I-SC110818), Deutsche Krebshilfe e. V. (107888; 109666), Open Access Publication Fund of University of Muenster and Wilhelm Sander-Stiftung (2009.041.1). W.E.B. is supported by Deutsche Forschungsgemeinschaft DFG EXC 1003 Cells in Motion—Cluster of Excellence.