title: Change in PD-L1 Expression After Acquiring Resistance to Gefitinib in EGFR-Mutant Non-Small-Cell Lung Cancer.
abstract: Therapies targeting programmed cell death-1 (PD-1) and its ligand (PD-L1) have been successful in a subset of patients with non-small-cell lung cancer (NSCLC). PD-L1 expression in tumor tissues has been suggested as a predictive and prognostic marker. We examined the change in PD-L1 expression after gefitinib in patients with EGFR-mutant NSCLC.
  
  
  
  Paired tumor tissues were collected before and after gefitinib from 18 patients. PD-L1 expression on the tumor and immune cells was defined by the H-score of immunohistochemical staining (range, 0-300). The correlations between the change in PD-L1 expression and clinicopathologic characteristics were analyzed.
  
  
  
  PD-L1 expression on tumor cells showed an increase in the median H-score from 25 to 40 (P = .067). Of the 18 patients, 7 (38.9%) had a marked increase in the median H-score (range, 80-180; group A) and 11 (61.1%) had no change in the median H-score (0 for both scores; group B). In groups A and B, the median progression-free survival for gefitinib was 13 and 12 months (P = .594), and the median overall survival was "not reached" and 38 months (P = .073), respectively. MET positivity by immunohistochemistry in biopsies after gefitinib therapy was significantly associated with group A (P = .028). The PD-L1 H-score by immunohistochemistry, but not by tumor cells, showed correlations with other immune cells; FOXP3(+) expression in biopsies before gefitinib use, and PD-1(+) and CD3(+) in biopsies after gefitinib therapy, respectively.
  
  
  
  PD-L1 expression in tumor cells markedly increased in a subset of patients after gefitinib treatment. Thus, rebiopsy should be considered when using PD-L1 expression as a biomarker.
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jae Joon
authors.initials: JJ
authors.lastname: Han
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea. Electronic address: kimdw@snu.ac.kr.
authors.forename: Dong-Wan
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul, Korea.
authors.forename: Jaemoon
authors.initials: J
authors.lastname: Koh
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Bhumsuk
authors.initials: B
authors.lastname: Keam
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Tae Min
authors.initials: TM
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul, Korea.
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Jeon
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Se-Hoon
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul, Korea.
authors.forename: Doo Hyun
authors.initials: DH
authors.lastname: Chung
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Dae Seog
authors.initials: DS
authors.lastname: Heo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000235:genetics / Q000378:metabolism*; D054316:Biomarkers, Pharmacological / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D000077156:Gefitinib; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011799:Quinazolines / Q000627:therapeutic use*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; D054316:Biomarkers, Pharmacological; C423236:CD274 protein, human; D011799:Quinazolines; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib
keywords: Epidermal growth factor receptor; Gefitinib; NSCLC; Programmed death receptor ligand-1; Tumor-infiltrating lymphocytes