title: Prolongation of overall survival in advanced lung adenocarcinoma patients with the XAGE1 (GAGED2a) antibody.
abstract: OBJECTIVE
  The cancer/testis antigen XAGE1 (GAGED2a) is expressed in approximately 40% of advanced lung adenocarcinomas. We investigated the clinical relevance of the XAGE1 (GAGED2a) immune responses in patients with advanced lung adenocarcinoma.
  
  
  METHODS
  The XAGE1 (GAGED2a) antigen expression and EGFR mutation were determined with tumor tissues. The XAGE1 (GAGED2a) antibody and T-cell immune responses, as well as immune cell phenotypes, were analyzed with blood samples. Patients with EGFR wild-type (EGFRwt) tumors were treated with conventional platinum-based doublet chemotherapy and patients with EGFR-mutated (EGFRmt) tumors were treated with EGFR-TKI and conventional chemotherapy. The overall survival (OS) rates of the antibody-positive and -negative patients were investigated.
  
  
  RESULTS
  The results showed that the OS of antibody-positive patients was prolonged significantly compared with that of antibody-negative patients with either XAGE1 (GAGED2a) antigen-positive EGFRwt (31.5 vs. 15.6 months, P = 0.05) or EGFRmt (34.7 vs. 11.1 months, P = 0.001) tumors. Multivariate analysis showed that the presence of the XAGE1 (GAGED2a) antibody was a strong predictor for prolonged OS in patients with XAGE1 (GAGED2a) antigen-positive tumors and in patients with either EGFRwt or EGFRmt tumors. On the other hand, XAGE1 (GAGED2a) antigen expression was a worse predictor in patients with EGFRmt tumors. Phenotypic and functional analyses of T cells indicated immune activation in the antibody-positive patients.
  
  
  CONCLUSIONS
  The findings suggest that production of the XAGE1 (GAGED2a) antibody predicts good prognosis for patients with lung adenocarcinoma as an immune biomarker and the protective effect of this naturally occurring immune response supports the concept of immunotherapy.
authors.affiliation: Department of Respiratory Medicine, Kawasaki Medical School, Kurashiki, Okayama, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ohue
authors.affiliation: Department of Respiratory Medicine, Kawasaki Medical School, Kurashiki, Okayama, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Kurose
authors.affiliation: Department of Respiratory Medicine, Kawasaki Medical School, Kurashiki, Okayama, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Mizote
authors.affiliation: Department of Respiratory Medicine, Kawasaki Medical School, Kurashiki, Okayama, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Matsumoto
authors.affiliation: Department of Respiratory Medicine, Kawasaki Medical School, Kurashiki, Okayama, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Nishio
authors.affiliation: Department of Respiratory Medicine, Kawasaki Medical School, Kurashiki, Okayama, Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Isobe
authors.affiliation: Nagasaki University Clinical Oncology Center, Nagasaki, Nagasaki, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Fukuda
authors.affiliation: Faculty of Health and Welfare, Kawasaki University of Medical Welfare, Kurashiki, Okayama, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Uenaka
authors.affiliation: Department of Respiratory Medicine, Kawasaki Medical School, Kurashiki, Okayama, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Oka
authors.affiliation: Faculty of Health and Welfare, Kawasaki University of Medical Welfare, Kurashiki, Okayama, Japan. nakayama@mw.kawasaki-m.ac.jp.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Nakayama
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000906:Antibodies / Q000097:blood / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D018450:Disease Progression; D066246:ErbB Receptors / Q000235:genetics; D006801:Humans; D016130:Immunophenotyping; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D008213:Lymphocyte Activation; D009154:Mutation; D009367:Neoplasm Staging; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D000906:Antibodies; D000951:Antigens, Neoplasm; C413656:XAGE1A protein, human; D066246:ErbB Receptors