Department of Gastroenterological Surgery and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Department of Diagnostic Pathology, Okayama University Hospital, Okayama, Japan.
Br J Cancer. 2022 Sep;127(4):757-765. doi: 10.1038/s41416-022-01838-y. Epub 2022 May 21.
Emerging evidence indicates that immunogenicity plays an important role in intrahepatic cholangiocarcinoma (ICC). Herein, we systematically evaluated the clinical relevance of immunogenicity in ICC.
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.
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 < 0.001, log-rank test). Furthermore, the FCR was higher in tumour-free lymph nodes in ICCs with lymph node metastases than in those without lymph node metastases (P = 0.003, Mann-Whitney U test).
FCR should be considered an important biomarker that represents the immune environment of ICC based on its potentially important role in tumour progression, especially lymph node metastasis.
新出现的证据表明，免疫原性在肝内胆管癌（ICC）中起着重要作用。在此，我们系统地评估了 ICC 中免疫原性的临床相关性。
在公共数据集和癌症免疫图谱（TCIA）中评估高免疫原性 ICC，以确定 ICC 及根治性切除后关键成分的免疫原性的预后影响。我们还研究了 ICC 中免疫微环境的临床相关性。
使用基因表达综合数据集 89749 和 TCIA，我们在高免疫原性 ICC 中鉴定了 CD8/叉头框 P3（FoxP3）肿瘤浸润淋巴细胞（TILs）、T 细胞免疫球蛋白和粘蛋白结构域 3（TIM-3）和人类白细胞抗原-A（HLA-A）。对内部队列的免疫组织化学分析表明，肿瘤内 FoxP3 TILs 与 CD8 TILs 相关（P=0.045，Fisher 确切检验），高 FoxP3/CD8 比值（FCR）是生存不良的重要标志物（P<0.001，对数秩检验）。此外，在有淋巴结转移的 ICC 中，无淋巴结转移的肿瘤内 FCR 高于肿瘤内 FCR（P=0.003，Mann-Whitney U 检验）。
FCR 应被视为一种重要的生物标志物，代表 ICC 的免疫环境，基于其在肿瘤进展，特别是淋巴结转移中的潜在重要作用。
