title: Programmed Death-Ligand 1 Expression Predicts Tyrosine Kinase Inhibitor Response and Better Prognosis in a Cohort of Patients With Epidermal Growth Factor Receptor Mutation-Positive Lung Adenocarcinoma.
abstract: BACKGROUND
  The immune checkpoint proteins programmed death-1/ligand (PD-1/PD-L1) play a critical role in immune escape of tumor cells. In models of epidermal growth factor receptor (EGFR)-driven non-small-cell lung cancer (NSCLC), EGFR signal upregulates PD-1/PD-L1. However, data on the clinical significance of PD1/PD-L1 expression in patients with the subtype of NSCLC carrying EGFR mutations remain limited.
  
  
  METHODS
  Immunohistochemistry was performed to evaluate the expression of PD-1, PD-L1, and CD4+ and CD8+ tumor-infiltrating T lymphocytes (TILs).
  
  
  RESULTS
  In a cohort of 56 patients, PD-L1 and PD-1 was positive in 53.6% and 32.1% of tumor specimens, respectively. PD-L1(+) patients had a significantly greater disease-control rate (P = .004), in association with longer progression-free survival (P = .001) after EGFR-tyrosine kinase inhibitor (TKI) therapy and overall survival (P = .004), and no correlation between PD-1 positivity and clinical outcomes was observed. PD-L1 expression was not significantly associated with either clinicopathologic features or TILs.
  
  
  CONCLUSIONS
  These findings suggest that this subtype of EGFR mutation-positive NSCLC is highly eligible for PD-1/PD-L1 immunotherapy. PD-L1 might represent a favorable biomarker candidate for the response to EGFR-TKIs and outcomes of these patients with NSCLC.
authors: Department of Oncology, Fuzhou General Hospital of Nanjing Military Command, Fuzong Clinical College of Fujian Medical University, Fuzhou, Fujian, China.
authors: Cheng
authors: C
authors: Lin
authors: Department of Oncology, Fuzhou General Hospital of Nanjing Military Command, Fuzong Clinical College of Fujian Medical University, Fuzhou, Fujian, China.
authors: Xiong
authors: X
authors: Chen
authors: Department of Oncology, Fujian Provincial Cancer Hospital, Jinan District, Fuzhou, Fujian, China.
authors: Meifang
authors: M
authors: Li
authors: Department of Oncology, Fuzhou General Hospital of Nanjing Military Command, Fuzong Clinical College of Fujian Medical University, Fuzhou, Fujian, China.
authors: Jingnan
authors: J
authors: Liu
authors: Department of Pathology, Fuzhou General Hospital of Nanjing Military Command, Fuzhou, Fujian, China.
authors: Xingfeng
authors: X
authors: Qi
authors: Department of Pathology, Fuzhou General Hospital of Nanjing Military Command, Fuzhou, Fujian, China.
authors: Wenting
authors: W
authors: Yang
authors: Department of Epidemiology and Health Statistics, Fujian Medical University School of Public Health, Fuzhou, Fujian, China.
authors: Hairong
authors: H
authors: Zhang
authors: Department of Oncology, 180th Hospital of People's Liberation Army, Quanzhou, Fujian, China.
authors: Zhongfu
authors: Z
authors: Cai
authors: Division of Hematology and Oncology, Department of Medicine, Virginia Commonwealth University, Massey Cancer Center, Richmond, VA.
authors: Yun
authors: Y
authors: Dai
authors: Department of Oncology, Fuzhou General Hospital of Nanjing Military Command, Fuzong Clinical College of Fujian Medical University, Fuzhou, Fujian, China. Electronic address: oyxn@public.fz.fj.cn.
authors: Xuenong
authors: X
authors: Ouyang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGFR mutation; EGFR-TKI therapy; Immunohistochemistry; Lung adenocarcinoma; PD-L1