title: Clinical Implications of Cytotoxic T Lymphocyte Antigen-4 Expression on Tumor Cells and Tumor-Infiltrating Lymphocytes in Extrahepatic Bile Duct Cancer Patients Undergoing Surgery Plus Adjuvant Chemoradiotherapy.
abstract: There currently is only limited knowledge on the role of tumor-specific immunity in cholangiocarcinoma.
  
  
  
  This study evaluated the clinical implications of cytotoxic T lymphocyte antigen-4 (CTLA-4) expression levels and CD4+and CD8+tumor-infiltrating lymphocytes (TILs) in extrahepatic bile duct (EHBD) cancer.
  
  
  
  Immunohistochemistry of CTLA-4, CD4, and CD8 was performed for 77 EHBD cancer patients undergoing surgery plus adjuvant chemoradiotherapy. CTLA-4 expression on tumor cells and TILs were assessed by using H-scores and the proportion of CTLA-4+lymphocytes, respectively.
  
  
  
  With optimal cutoff values determined by a maximal chi-square method with overall survival (OS) data, patients with CTLA-4 H-score >70 and a proportion of CTLA-4+TILs >0.15 showed higher mean density of CD8+and CD4+TILs, respectively (P = 0.025 for CD8+and P = 0.055 for CD4+TILs). The high CTLA-4 H-score level was associated with prolonged OS and disease-free interval (DFI) (P = 0.025 and 0.004, respectively). With differential levels of CTLA-4 H-score according to hilar and non-hilar locations (high rate 32 vs. 68%, respectively; P = 0.013), an exploratory subgroup analysis demonstrated that the associations between the CTLA-4 expression and OS and DFI were confined to hilar tumors (P = 0.003 and <0.001, respectively), but not to non-hilar ones (P = 0.613 and 0.888, respectively).
  
  
  
  This study demonstrates a potential prognostic relevance of CTLA-4 expression in EHBD cancer. We suggest a differential survival impact of the CTLA-4 expression level according to different tumor locations.
authors.affiliation: Department of Radiation Oncology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea.
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Lim
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea.
authors.forename: Jaemoon
authors.initials: J
authors.lastname: Koh
authors.affiliation: Department of Radiation Oncology, Ewha Womans University School of Medicine, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul, 158-710, Republic of Korea. kyubokim.ro@gmail.com.
authors.forename: Kyubo
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Radiation Oncology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea.
authors.forename: Eui Kyu
authors.initials: EK
authors.lastname: Chie
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea.
authors.forename: Sehui
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea.
authors.forename: Kyoung Bun
authors.initials: KB
authors.lastname: Lee
authors.affiliation: Department of Surgery, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea.
authors.forename: Jin-Young
authors.initials: JY
authors.lastname: Jang
authors.affiliation: Department of Surgery, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea.
authors.forename: Sun Whe
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea.
authors.forename: Do-Youn
authors.initials: DY
authors.lastname: Oh
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea.
authors.forename: Yung-Jue
authors.initials: YJ
authors.lastname: Bang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017734:Bile Ducts, Extrahepatic / Q000187:drug effects / Q000276:immunology* / Q000601:surgery; D060908:CTLA-4 Antigen / Q000378:metabolism*; D059186:Chemoradiotherapy, Adjuvant / Q000379:methods*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism*; D008875:Middle Aged; D012189:Retrospective Studies; D046888:Tissue Array Analysis
chemical_list: D060908:CTLA-4 Antigen