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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

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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.

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Author notes

    Authors and Affiliations

    1. Department of Radiation Oncology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea

      Yu Jin Lim & Eui Kyu Chie

    2. Department of Pathology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea

      Jaemoon Koh, Sehui Kim & Kyoung Bun Lee

    3. Department of Radiation Oncology, Ewha Womans University School of Medicine, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul, 158-710, Republic of Korea

      Kyubo Kim

    4. Department of Surgery, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea

      Jin-Young Jang & Sun Whe Kim

    5. Department of Internal Medicine, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea

      Do-Youn Oh & Yung-Jue Bang

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    1. Yu Jin Lim
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    Correspondence to Kyubo Kim.

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    Yu Jin Lim and Jaemoon Koh contributed equally to this work.

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    Lim, Y.J., Koh, J., Kim, K. et al. 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. Targ Oncol 12, 211–218 (2017). https://doi.org/10.1007/s11523-016-0474-1

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    • DOI: https://doi.org/10.1007/s11523-016-0474-1

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