방사선의학 웹진

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그림1 . 대표 슬라이드 단면 사진. CTLA-4 H-score (x 400): (a) low and (b) high. Proportion of CTLA-4+ tumor-infiltrating lymphocytes (TILs) (x 400): (c) low and (d) high. CD4 and CD8 views for the ratio of CD4+/CD8+ TILs (x 1000): (e-f) low ratio, (g-h): high ratio. a-d의 네모 상자는 각각의 확대 결과이며, scale bar는 50μm 기준임.

​그림2 . CTLA-4 발현 수준에 따른 TILs density 차이. (a) CTLA-4 H-score와 CD8+ TILs 관계 (b) 종양 침윤 림프구 내 CTLA-4 발현과 CD4+ TILs 관계.​

그림3 . CTLA-4 H-score에 따른 (a) overall survival 및 (b) disease-free interval.​

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.​ 

Author information

Lim YJ1, Koh J2, Kim K3, Chie EK1, Kim S2, Lee KB2, Jang JY4, Kim SW4, Oh DY5, Bang YJ5.​

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

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

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

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

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