Programmed death ligand-1 expression in non-small cell lung cancer.
Recent strategies targeting the interaction of the programmed cell death ligand-1 (PD-L1, B7-H1, CD274) with its receptor, PD-1, resulted in promising activity in early phase clinical trials. In this study, we used various antibodies and in situ mRNA hybridization to measure PD-L1 in non-small cell lung cancer (NSCLC) using a quantitative fluorescence (QIF) approach to determine the frequency of expression and prognostic value in two independent populations. A control tissue microarray (TMA) was constructed using PD-L1-transfected cells, normal human placenta and known PD-L1-positive NSCLC cases. Only one of four antibodies against PD-L1 (5H1) validated for specificity on this TMA. In situ PD-L1 mRNA using the RNAscope method was similarly validated. Two cohorts of NSCLC cases in TMAs including 340 cases from hospitals in Greece and 204 cases from Yale University were assessed. Tumors showed PD-L1 protein expression in 36% (Greek) and 25% (Yale) of the cases. PD-L1 expression was significantly associated with tumor-infiltrating lymphocytes in both cohorts. Patients with PD-L1 (both protein and mRNA) expression above the detection threshold showed statistically significant better outcome in both series (log-rank P=0.036 and P=0.027). Multivariate analysis showed that PD-L1 expression was significantly associated with better outcome independent of histology. Measurement of PD-L1 requires specific conditions and some commercial antibodies show lack of specificity. Expression of PD-L1 protein or mRNA is associated with better outcome. Further studies are required to determine the value of this marker in prognosis and prediction of response to treatments targeting this pathway.
Solid Tumor, Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
Vamsidhar
V
Velcheti
Department of Pathology, Yale School of Medicine, New Haven, CT, USA.
Kurt A
KA
Schalper
Department of Pathology, Yale School of Medicine, New Haven, CT, USA.
Daniel E
DE
Carvajal
Department of Medical Oncology, Yale School of Medicine, New Haven, CT, USA.
Valsamo K
VK
Anagnostou
1] Department of Medical Oncology, Yale School of Medicine, New Haven, CT, USA [2] Oncology Unit, Department of Medicine, University of Athens, Sotiria General Hospital, Athens, Greece.
Konstantinos N
KN
Syrigos
Department of Medical Oncology, Yale School of Medicine, New Haven, CT, USA.
Mario
M
Sznol
Department of Medical Oncology, Yale School of Medicine, New Haven, CT, USA.
Roy S
RS
Herbst
Department of Medical Oncology, Yale School of Medicine, New Haven, CT, USA.
Scott N
SN
Gettinger
1] Department of Medical Oncology, Yale School of Medicine, New Haven, CT, USA [2] Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA.
Lieping
L
Chen
Department of Pathology, Yale School of Medicine, New Haven, CT, USA.
David L
DL
Rimm
D000368:Aged; D060890:B7-H1 Antigen / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D016009:Chi-Square Distribution; D015331:Cohort Studies; D003237:Connecticut; D005260:Female; D006115:Greece; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008297:Male; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D016019:Survival Analysis; D046888:Tissue Array Analysis
D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; D012333:RNA, Messenger