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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
- 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
- Lim, Yu Jin; Koh, Jaemoon; Kim, Kyubo; Chie, Eui Kyu; Kim, Sehui; Lee, Kyoung Bun; Jang, Jin-Young; Kim, Sun Whe; Oh, Do-Youn; Bang, Yung-Jue
- Ewha Authors
- SCOPUS Author ID
- Issue Date
- Journal Title
- TARGETED ONCOLOGY
- 1776-2596; 1776-260X
- vol. 12, no. 2, pp. 211 - 218
- SCIE; SCOPUS
- 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.
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