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

Schmidt Lars Henning, Kümmel Andreas , Görlich Dennis, Mohr Michael, Bröckling Sebastian, Mikesch Jan Henrik, Grünewald Inga, Marra Alessandro, Schultheis Anne M, Wardelmann Eva , Müller-Tidow Carsten, Spieker Tilmann, Schliemann Christoph, Berdel Wolfgang E, Wiewrodt Rainer, Hartmann Wolfgang

Abstract

Background Immunotherapy can become a crucial therapeutic option to improve prognosis for lung cancerpatients. First clinical trials with therapies targeting the programmed cell death receptorPD-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 factorsremains unclear. Method The impact of both factors was evaluated in a study collective of 321 clinically well-annotatedpatients with non-small lung cancer (NSCLC) using immunohistochemistry. Results PD-1 expression by tumor infiltrating lymphocytes (TILs) was found in 22%, whereas tumorcell associated PD-L1 expression was observed in 24%of the NSCLC tumors. In Fisher'sexact 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 survivalin 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 regressionmodels. Conclusion One major finding of our study is the identification of a prognostic implication of PD-L1 insubsets of NSCLC patients with pulmonary SCC, with increased tumor size, with a positivelymph node status and NSCLC patients who received adjuvant therapies. This study providesfirst data for immune-context related risk stratification of NSCLC patients. Furtherstudies are necessary both to confirm this observation and to evaluate the predictive valueof PD-1 and PD-L1 in NSCLC in the context of PD-1 inhibition.