title: PD-1 and PD-L1 expression in molecularly selected non-small-cell lung cancer patients.
abstract: BACKGROUND
  Agents targeting programmed death-1 receptor (PD-1) and its ligand (PD-L1) are showing promising results in non-small-cell lung cancer (NSCLC). It is unknown whether PD-1/PD-L1 are differently expressed in oncogene-addicted NSCLC.
  
  
  METHODS
  We analysed a cohort of 125 NSCLC patients, including 56 EGFR mutated, 29 KRAS mutated, 10 ALK translocated and 30 EGFR/KRAS/ALK wild type. PD-L1 and PD-1 expression were assessed by immunohistochemistry. All cases with moderate or strong staining (2+/3+) in >5% of tumour cells were considered as positive.
  
  
  RESULTS
  PD-1 positive (+) was significantly associated with current smoking status (P=0.02) and with the presence of KRAS mutations (P=0.006), whereas PD-L1+ was significantly associated to adenocarcinoma histology (P=0.005) and with presence of EGFR mutations (P=0.001). In patients treated with EGFR tyrosine kinase inhibitors (N=95), sensitivity to gefitinib or erlotinib was higher in PD-L1+ vs PD-L1 negative in terms of the response rate (RR: P=0.01) time to progression (TTP: P<0.0001) and survival (OS: P=0.09), with no difference in PD1+ vs PD-1 negative. In the subset of 54 EGFR mutated patients, TTP was significantly longer in PD-L1+ than in PD-L1 negative (P=0.01).
  
  
  CONCLUSIONS
  PD-1 and PD-L1 are differentially expressed in oncogene-addicted NSCLC supporting further investigation of specific checkpoint inhibitors in combination with targeted therapies.
authors.affiliation: Department of Medical Oncology, Istituto Toscano Tumori, Civil Hospital, Viale Alfieri 36, 57124 Livorno, Italy.
authors.forename: A
authors.initials: A
authors.lastname: D'Incecco
authors.affiliation: Department of Pathology, Basel Hospital University, Schönbeinstrasse 40, 4003 Basel, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Andreozzi
authors.affiliation: Division of Medical Oncology, Santa Maria della Misericordia Hospital, Località S. Andrea delle Fratte 1, 06134 Perugia, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Ludovini
authors.affiliation: Department of Medical Oncology, Istituto Toscano Tumori, Civil Hospital, Viale Alfieri 36, 57124 Livorno, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Rossi
authors.affiliation: Azienda Ospedaliero-Universitaria Pisana, University Hospital, via Roma 57, 56126 Pisa, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Capodanno
authors.affiliation: Department of Medical Oncology, Istituto Toscano Tumori, Civil Hospital, Viale Alfieri 36, 57124 Livorno, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Landi
authors.affiliation: Department of Medical Oncology, Istituto Toscano Tumori, Civil Hospital, Viale Alfieri 36, 57124 Livorno, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Tibaldi
authors.affiliation: Department of Medical Oncology, Istituto Toscano Tumori, Civil Hospital, Viale Alfieri 36, 57124 Livorno, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Minuti
authors.affiliation: Department of Medical Oncology, Istituto Toscano Tumori, Civil Hospital, Viale Alfieri 36, 57124 Livorno, Italy.
authors.forename: J
authors.initials: J
authors.lastname: Salvini
authors.affiliation: Department of Medical Oncology, Istituto Toscano Tumori, Civil Hospital, Viale Alfieri 36, 57124 Livorno, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Coppi
authors.affiliation: Azienda Ospedaliero-Universitaria Pisana, University Hospital, via Roma 57, 56126 Pisa, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Chella
authors.affiliation: Department of Surgical, Medical, Molecular Pathology and Critical Area, Pisa University, via Roma 57, 56126 Pisa, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Fontanini
authors.affiliation: Department of Medical Oncology, Istituto Toscano Tumori, Civil Hospital, Viale Alfieri 36, 57124 Livorno, Italy.
authors.forename: M E
authors.initials: ME
authors.lastname: Filice
authors.affiliation: Department of Pathology, Basel Hospital University, Schönbeinstrasse 40, 4003 Basel, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: Tornillo
authors.affiliation: Department of Medical Oncology, Istituto Toscano Tumori, Civil Hospital, Viale Alfieri 36, 57124 Livorno, Italy.
authors.forename: R M
authors.initials: RM
authors.lastname: Incensati
authors.affiliation: Department of Medical Oncology, Istituto Toscano Tumori, Civil Hospital, Viale Alfieri 36, 57124 Livorno, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Sani
authors.affiliation: Division of Medical Oncology, Santa Maria della Misericordia Hospital, Località S. Andrea delle Fratte 1, 06134 Perugia, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Crinò
authors.affiliation: Department of Pathology, Basel Hospital University, Schönbeinstrasse 40, 4003 Basel, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: Terracciano
authors.affiliation: Department of Medical Oncology, Istituto Toscano Tumori, Civil Hospital, Viale Alfieri 36, 57124 Livorno, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Cappuzzo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000096:biosynthesis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000096:biosynthesis*; D012189:Retrospective Studies
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor