Regulatory T cells induce a suppressive immune milieu and promote lymph node metastasis in intrahepatic cholangiocarcinoma

Background Emerging evidence indicates that immunogenicity plays an important role in intrahepatic cholangiocarcinoma (ICC). Herein, we systematically evaluated the clinical relevance of immunogenicity in ICC. Methods Highly immunogenic ICCs identified in the public dataset and the Cancer Immunome A...

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Bibliographic Details
Published in:British journal of cancer 2022-09, Vol.127 (4), p.757-765
Main Authors: Konishi, Daisuke, Umeda, Yuzo, Yoshida, Kazuhiro, Shigeyasu, Kunitoshi, Yano, Shuya, Toji, Tomohiro, Takeda, Sho, Yoshida, Ryuichi, Yasui, Kazuya, Fuji, Tomokazu, Matsumoto, Kazuyuki, Kishimoto, Hiroyuki, Michiue, Hiroyuki, Teraishi, Fuminori, Kato, Hironari, Tazawa, Hiroshi, Yanai, Hiroyuki, Yagi, Takahito, Goel, Ajay, Fujiwara, Toshiyoshi
Format: Article
Language:English
Subjects:
631/250/580
631/67/1504/1610
Biomedical and Life Sciences
Biomedicine
Cancer Research
CD8 antigen
Cholangiocarcinoma
Drug Resistance
Epidemiology
Forkhead protein
Foxp3 protein
Gene expression
Histocompatibility antigen HLA
Immunogenicity
Immunoregulation
Lymph nodes
Lymphatic system
Lymphocytes T
Metastases
Metastasis
Molecular Medicine
Mucin
Oncology
Tumors
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Summary:Background Emerging evidence indicates that immunogenicity plays an important role in intrahepatic cholangiocarcinoma (ICC). Herein, we systematically evaluated the clinical relevance of immunogenicity in ICC. Methods Highly immunogenic ICCs identified in the public dataset and the Cancer Immunome Atlas (TCIA) were assessed to determine the prognostic impact of immunogenicity in ICC and key components after curative resection. We also investigated the clinical relevance of the immune milieu in ICC. Results Using the Gene Expression Omnibus dataset 89749 and TCIA, we identified CD8 + /forkhead box P3 (FoxP3) + tumour-infiltrating lymphocytes (TILs), T-cell immunoglobulin and mucin domain 3 (TIM-3) and human leukocyte antigen-A (HLA-A) in highly immunogenic ICCs. Immunohistochemical analysis of the in-house cohort showed that intratumoral FoxP3 + TILs correlated with CD8 + TILs ( P  = 0.045, Fisher’s exact test) and that high FoxP3 + /CD8 + ratio (FCR) was an important marker for poor survival ( P  
ISSN:0007-0920
1532-1827
DOI:10.1038/s41416-022-01838-y