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
1.Department of Radiation Oncology,Seoul National University College of Medicine,Seoul,Republic of Korea;2.Department of Pathology,Seoul National University College of Medicine,Seoul,Republic of Korea;3.Department of Radiation Oncology,Ewha Womans University School of Medicine,Seoul,Republic of Korea;4.Department of Surgery,Seoul National University College of Medicine,Seoul,Republic of Korea;5.Department of Internal Medicine,Seoul National University College of Medicine,Seoul,Republic of Korea
Abstract:
Background
There currently is only limited knowledge on the role of tumor-specific immunity in cholangiocarcinoma.
Objective
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.
Patients and Methods
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.
Results
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).
Conclusions
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.
