글로벌 연구동향
방사선종양학
- 2017년 05월호
[Target Oncol. ] 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.이화의대 / 임유진, 고재문, 김규보*
- 출처
- Target Oncol.
- 등재일
- 2017 Apr
- 저널이슈번호
- 12(2):211-218. doi: 10.1007/s11523-016-0474-1.
- 내용
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.
그림4. 종양 위치에 따른 CTLA-4 H-score의 예후 관련성을 분석한 forest plot.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.
1 Department of Radiation Oncology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea.
2 Department of Pathology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea.
3 Department of Radiation Oncology, Ewha Womans University School of Medicine, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul, 158-710, Republic of Korea. kyubokim.ro@gmail.com.
4 Department of Surgery, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea.
5 Department of Internal Medicine, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea.
- 연구소개
- CTLA-4는 T 세포 활성 항원의 일종으로서 종양 면역 반응을 저하시키는 억제조절자의 기능으로 잘 알려져 있습니다. 하지만 종양 세포 및 종양 침윤 림프구에서의 발현과 임상적 의의에 대해서는 잘 알려져 있지 않습니다. 본 연구는 수술 후 항암방사선 치료를 시행 받은 간외담도암 환자 검체의 CTLA-4, CD4, CD8 면역조직화학염색을 통해 종양 세포에서의 CTLA-4 발현이 높은 환자군에서 더 나은 생존 결과를 확인했습니다. 또한 종양의 세부 위치에 따라 CTLA-4 발현도 및 그에 따른 예후 관련성이 달라짐을 관찰했습니다. 본 결과들은 종양 세포 자체와 종양 침윤 림프구에서의 CTLA-4 발현을 종합적으로 분석했다는 점, 그리고 CD4 및 CD8 양성 림프구 수준과의 관련성을 함께 살펴보았다는 점에서 의의가 있으며, 이를 통해 간외담도암에서의 CTLA-4 관련 면역학적 특징과 그에 따른 임상적 관련성에 대해 고찰해볼 수 있었습니다.
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