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
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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.
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.
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).
KeywordsOverall Survival Cholangiocarcinoma Ipilimumab Extrahepatic Bile Duct Biliary Tract Cancer
Compliance with Ethical Standards
Conflict of Interest
The authors declare no conflicts of interest.
- 2.American Cancer Society. Bile duct cancer (cholangiocarcinoma). 2016. http://www.cancer.org/acs/groups/cid/documents/webcontent/003084-pdf.pdf. Accessed 29 Sept 2016.
- 4.Kim MY, Kim JH, Kim Y, Byun SJ. Postoperative radiotherapy appeared to improve the disease free survival rate of patients with extrahepatic bile duct cancer at high risk of loco-regional recurrence. Radiat Oncol J. 2016;34:297–304.Google Scholar
- 15.Lim YJ, Koh J, Kim K, et al. High ratio of programmed cell death protein 1 (PD-1)(+)/CD8(+) tumor-infiltrating lymphocytes identifies a poor prognostic subset of extrahepatic bile duct cancer undergoing surgery plus adjuvant chemoradiotherapy. Radiother Oncol. 2015;117:165–70.CrossRefPubMedGoogle Scholar
- 16.Hothorn T, Lausen B. On maximally selected rank statistics. R News. 2002;2:3–5.Google Scholar
- 26.Cadamuro M, Morton SD, Strazzabosco M, Fabris L. Unveiling the role of tumor reactive stroma in cholangiocarcinoma: an opportunity for new therapeutic strategies. Transl Gastrointest Cancer. 2013;2:130–44.Google Scholar