干旱区生态环境知识资源中心(Arid): Identification of Four Immune Subtypes Characterized by Distinct Composition and Functions of Tumor Microenvironment in Intrahepatic Cholangiocarcinoma

Arid

DOI	10.1002/hep.31092
	Identification of Four Immune Subtypes Characterized by Distinct Composition and Functions of Tumor Microenvironment in Intrahepatic Cholangiocarcinoma
	Job, Sylvie; Rapoud, Delphine; Dos Santos, Alexandre; Gonzalez, Patrick; Desterke, Christophe; Pascal, Gerard; Elarouci, Nabila; Ayadi, Mira; Adam, Rene; Azoulay, Daniel; Castaing, Denis; Vibert, Eric; Cherqui, Daniel; Samuel, Didier; Sa Cuhna, Antonio; Marchio, Agnes; Pineau, Pascal; Guettier, Catherine; de Reynies, Aurelien; Faivre, Jamila
通讯作者	Faivre, J
来源期刊	HEPATOLOGY
ISSN	0270-9139
EISSN	1527-3350
出版年	2020
卷号	72 期号:3 页码:965-981
英文摘要	Background and Aims Intrahepatic cholangiocarcinoma (ICC) is a severe malignant tumor in which the standard therapies are mostly ineffective. The biological significance of the desmoplastic tumor microenvironment (TME) of ICC has been stressed but was insufficiently taken into account in the search for classifications of ICC adapted to clinical trial design. We investigated the heterogeneous tumor stroma composition and built a TME-based classification of ICC tumors that detects potentially targetable ICC subtypes. Approach and Results We established the bulk gene expression profiles of 78 ICCs. Epithelial and stromal compartments of 23 ICCs were laser microdissected. We quantified 14 gene expression signatures of the TME and those of 3 functional indicators (liver activity, inflammation, immune resistance). The cell population abundances were quantified using the microenvironment cell population-counter package and compared with immunohistochemistry. We performed an unsupervised TME-based classification of 198 ICCs (training set) and 368 ICCs (validation set). We determined immune response and signaling features of the different immune subtypes by functional annotations. We showed that a set of 198 ICCs could be classified into 4 TME-based subtypes related to distinct immune escape mechanisms and patient outcomes. The validity of these immune subtypes was confirmed over an independent set of 368 ICCs and by immunohistochemical analysis of 64 ICC tissue samples. About 45% of ICCs displayed an immune desert phenotype. The other subtypes differed in nature (lymphoid, myeloid, mesenchymal) and abundance of tumor-infiltrating cells. The inflamed subtype (11%) presented a massive T lymphocyte infiltration, an activation of inflammatory and immune checkpoint pathways, and was associated with the longest patient survival. Conclusion We showed the existence of an inflamed ICC subtype, which is potentially treatable with checkpoint blockade immunotherapy.
类型	Article
语种	英语
开放获取类型	Other Gold, Green Published
收录类别	SCI-E
WOS记录号	WOS:000559903600001
WOS关键词	EPITHELIAL-MESENCHYMAL TRANSITION ; HEPATIC STELLATE CELLS ; MOLECULAR SUBTYPES ; PROFILING REVEALS ; CANCER ; IPILIMUMAB ; EXPRESSION ; NIVOLUMAB ; TARGETS
WOS类目	Gastroenterology & Hepatology
WOS研究方向	Gastroenterology & Hepatology
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/325636
作者单位	[Job, Sylvie; Elarouci, Nabila; Ayadi, Mira; de Reynies, Aurelien] Ligue Natl Canc, Programme Cartes Ident Tumeurs, Paris, France; [Rapoud, Delphine; Dos Santos, Alexandre; Gonzalez, Patrick; Pascal, Gerard; Adam, Rene; Azoulay, Daniel; Castaing, Denis; Vibert, Eric; Cherqui, Daniel; Samuel, Didier; Sa Cuhna, Antonio; Guettier, Catherine; Faivre, Jamila] Paul Brousse Univ Hosp, Hepatobiliary Ctr, INSERM, U1193, Villejuif, France; [Rapoud, Delphine; Dos Santos, Alexandre; Gonzalez, Patrick; Desterke, Christophe; Pascal, Gerard; Adam, Rene; Azoulay, Daniel; Castaing, Denis; Vibert, Eric; Cherqui, Daniel; Samuel, Didier; Sa Cuhna, Antonio; Guettier, Catherine; Faivre, Jamila] Univ Paris Saclay, Fac Med Kremlin Bicetre, Univ Paris Sud, Le Kremlin Bicetre, France; [Marchio, Agnes; Pineau, Pascal] Inst Pasteur, Unite Org Nucl & Oncogenese, INSERM, U993, Paris, France; [Guettier, Catherine] Kremlin Bicetre Hosp, Assistance Publ Hop Paris AP HP, Dept Pathol, Le Kremlin Bicetre, France; [Faivre, Jamila] Paul Brous...
推荐引用方式 GB/T 7714	Job, Sylvie,Rapoud, Delphine,Dos Santos, Alexandre,et al. Identification of Four Immune Subtypes Characterized by Distinct Composition and Functions of Tumor Microenvironment in Intrahepatic Cholangiocarcinoma[J],2020,72(3):965-981.
APA	Job, Sylvie.,Rapoud, Delphine.,Dos Santos, Alexandre.,Gonzalez, Patrick.,Desterke, Christophe.,...&Faivre, Jamila.(2020).Identification of Four Immune Subtypes Characterized by Distinct Composition and Functions of Tumor Microenvironment in Intrahepatic Cholangiocarcinoma.HEPATOLOGY,72(3),965-981.
MLA	Job, Sylvie,et al."Identification of Four Immune Subtypes Characterized by Distinct Composition and Functions of Tumor Microenvironment in Intrahepatic Cholangiocarcinoma".HEPATOLOGY 72.3(2020):965-981.