Programmed death ligand 1 expression in early stage, resectable non-small cell lung cancer

// Manolo D’Arcangelo 1 , Armida D’Incecco 2 , Claudia Ligorio 3 , Stefania Damiani 3 , Maurizio Puccetti 4 , Sara Bravaccini 5 , Luigi Terracciano 6 , Chiara Bennati 1 , Gabriele Minuti 1 , Silvia Vecchiarelli 1 , Lorenza Landi 1 , Marina Milesi 7 , Alberto Meroni 8 , Sara Ravaioli 5 , Maria Maddalena Tumedei 5 , Matteo Incarbone 8 and Federico Cappuzzo 1 1 AUSL della Romagna, Department of Oncology-Hematology, Ravenna, Italy 2 University Hospital of Siena, Medical Oncology and Immunotherapy, Center for Immuno-Oncology, Siena, Italy 3 University of Bologna, DIMES, Pathology, Bologna, Italy 4 AUSL della Romagna, Department of Pathology, Ravenna, Italy 5 Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCSS, Bioscences Laboratory, Meldola, Italy 6 University Hospital Basel, Institute of Pathology, Basel, Switzerland 7 Clinica San Carlo, Service of Pathology, Paderno Dugnano, Italy 8 RCCS MultiMedica, Thoracic Surgery, Sesto S.G., Italy Correspondence to: Federico Cappuzzo, email: federico.cappuzzo@auslromagna.it Keywords: PD-L1; NSCLC; prognosis; tumor grading Received: April 25, 2018     Accepted: December 10, 2018     Published: January 15, 2019 ABSTRACT Introduction: For several years non-small cell lung cancer (NSCLC) has been considered non-immunogenic. Recent advances in antitumor immunity brought to the discovery of checkpoints that modulate immune response against cancer. One of them is programmed death receptor 1 (PD-1) and its ligand (PD-L1). Although PD-L1 expression seems predictive of response to anti-PD-1/PD-L1 agents, its prognostic value is unclear. In this study we investigated the prognostic value of PD-L1 expression and its correlation with clinical-pathological characteristics in a cohort of surgically resected NSCLC. Material and methods: PD-L1 expression was evaluated in 289 surgically resected NSCLC samples by immunohistochemistry. Our cohort included patients not exposed to adjuvant chemotherapy. PD-L1 status was defined as: 1) PD-L1 high (tumor proportion score, TPS≥50%), PD-L1 low (TPS 1-49%), PD-L1 negative (TPS<1%); 2) PD-L1 positive (TPS≥50%) and negative (TPS<50%); 3) as a continuous variable. Results: Patients were mostly males (79%), former or current smokers (81%), with a median age of 67 years, non-squamous histology (67.5%) and high-grade tumors (55%). PD-L1 tumors were 18.7%. There was no significant association with sex, age, smoking status and histology. A strong correlation between high PD-L1 expression and tumor grade was detected. The difference in median OS in the different groups of patients was not statistically significant. Conclusion: PD-L1 is not prognostic in surgically resected NSCLC. The association with tumor differentiation suggests that grading could represent an easy-to-assess tool for selecting subjects potentially sensitive to immunotherapy warranting further investigations.