期刊
HEPATOLOGY
卷 75, 期 5, 页码 1154-1168出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1002/hep.32222
关键词
-
资金
- Swedish Research Council
- Swedish Cancer Society
- Swedish Foundation for Strategic Research
- Cancer Research Foundations of Radiumhemmet
- Knut and Alice Wallenberg Foundation
- Novo Nordisk Foundation
- Center for Innovative Medicine at Karolinska Institutet
- Stockholm County Council
- Karolinska Institutet
- Fundacao para a Ciencia e a Tecnologia [SFRH/ BD/85290/2012]
- Programa Operacional Potencial Humano- Quadro de Referencia Estrategico Nacional
- European Social Fund
- Fundação para a Ciência e a Tecnologia [SFRH/BD/85290/2012] Funding Source: FCT
The study found that MAIT cells were heterogenously lost from intrahepatic and perihilar cholangiocarcinoma tumors possibly in response to increased bacterial burden, while the residual intratumoral MAIT cells exhibited preserved receptor repertoire for interaction with tumor cells. The high presence of MAIT cells in the livers of iCCA patients predicted long-term survival and was associated with a favorable antitumor immune signature.
Background and Aims Cholangiocarcinoma (CCA) is a malignancy arising from biliary epithelial cells of intra- and extrahepatic bile ducts with dismal prognosis and few nonsurgical treatments available. Despite recent success in the immunotherapy-based treatment of many tumor types, this has not been successfully translated to CCA. Mucosal-associated invariant T (MAIT) cells are cytotoxic innate-like T cells highly enriched in the human liver, where they are located in close proximity to the biliary epithelium. Here, we aimed to comprehensively characterize MAIT cells in intrahepatic (iCCA) and perihilar CCA (pCCA). Approach and Results Liver tissue from patients with CCA was used to study immune cells, including MAIT cells, in tumor-affected and surrounding tissue by immunohistochemistry, RNA-sequencing, and multicolor flow cytometry. The iCCA and pCCA tumor microenvironment was characterized by the presence of both cytotoxic T cells and high numbers of regulatory T cells. In contrast, MAIT cells were heterogenously lost from tumors compared to the surrounding liver tissue. This loss possibly occurred in response to increased bacterial burden within tumors. The residual intratumoral MAIT cell population exhibited phenotypic and transcriptomic alterations, but a preserved receptor repertoire for interaction with tumor cells. Finally, the high presence of MAIT cells in livers of iCCA patients predicted long-term survival in two independent cohorts and was associated with a favorable antitumor immune signature. Conclusions MAIT cell tumor infiltration associates with favorable immunological fitness and predicts survival in CCA.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据