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Immune cell atlas of cholangiocarcinomas reveals distinct tumor microenvironments and associated prognoses.

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资源类型：
Pubmed体系：
作者：
Xia Tao[1,2,3,4] * ; Li Keyu[1,2,3,5] ; Niu Nan[1,2,3,4] ; Shao Yingkuan[1,2,3,6] ; Ding Ding[1,2,3] ; Thomas Dwayne L[1,7,2,3,8] ; Jing Hao[1,2] ; Fujiwara Kenji[1,2,3] ; Hu Haijie[1,2,3] ; Osipov Arsen[1,2,3] ; Yuan Chunhui[1,7,2,3] ; Wolfgang Christopher L[1,7,2,3] ; Thompson Elizabeth D[1,2,3,8] ; Anders Robert A[1,2,9,3,8] ; He Jin[1,7,2,3] ; Mou Yiping[4] ; Murphy Adrian G[1,2,3] ; Zheng Lei[10,11,12,13,14] ;
机构： [1]Department of Oncology, Johns Hopkins University School of Medicine,1650 Orleans Street, CRB1 Room 351, Baltimore, MD 21231, USA [2]Departmentof Surgery, Johns Hopkins University School of Medicine, Baltimore, MD,USA [3]The Sidney Kimmel Cancer Center, Johns Hopkins University Schoolof Medicine, Baltimore, MD, USA [4]The Bloomberg‑Kimmel Institute for CancerImmunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA [5]The Pancreatic Cancer Precision Medicine Center of ExcellenceProgram, Johns Hopkins University School of Medicine, Baltimore, MD, USA [6]Department of Pathology, Johns Hopkins University School of Medicine,Baltimore, MD, USA [7]Present Address: Department of Gastrointestinaland Pancreatic Surgery, Department of General Surgery, and Cancer Center,The Zhejiang Provincial People’s Hospital and the Affiliated People’s Hospitalof Hangzhou Medical College, Hangzhou, China [8]Present Address: Departmentof Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu,China [9]Present Address: The Zhejiang University Second Affiliated Hospital,Hangzhou, China
出处：
DOI： 10.1186/s13045-022-01253-z

关键词： Cholangiocarcinoma Tumor microenvironment PD-1 PD-L1 Effector T cells T regulator cells Myeloid cells Tumor-associated macrophages Multiplex immunohistochemistry

摘要：
Immunotherapy has demonstrated a limited clinical efficacy in approximately 5% of cholangiocarcinoma. The main challenges for an effective immunotherapy response in cholangiocarcinoma arise from the tumor microenvironment, which is poorly understood.For a comprehensive analysis of the tumor microenvironment in cholangiocarcinoma, we performed multiplex immunohistochemistry with two 15-marker immune panels and Nanostring assays for a comprehensive analysis of 104 surgically resected cholangiocarcinomas including intrahepatic, hilar, and distal cholangiocarcinoma. We also validated some key findings with a batch integration analysis of published single cell RNA sequencing data.This study found that natural killer cells occupy the largest immune cell compartment in cholangiocarcinoma. Granzyme-B+CD8+ effector T cells are significantly associated with better overall survival in both intrahepatic and distal cholangiocarcinoma. Above 85% of intrahepatic cholangiocarcinomas with higher density of PD-1-EOMES-CD8+ effector T cells are associated with long-term survival. However, only the density of PD-1-EOMES-CD8+ T cells in the tumor areas, but not in the peripheries of the tumors, is prognostic. In all three cholangiocarcinoma subtypes, T regulator cells are significantly associated with a poor prognosis; however, M1 and M2 tumor-associated macrophages or PD-L1+ tumor-associated macrophage demonstrate different prognostic values. Combining PD-L1+ M1 or M2, PD-L1- M1 or M2 tumor-associated macrophages, and T regulator cells to subgroup intrahepatic and distal cholangiocarcinoma, the prognosis is significantly better distinguished. Moreover, PD-L1- M2 tumor-associated macrophages is associated with a good prognosis in intrahepatic and distal cholangiocarcinoma, suggesting this subtype of M2 tumor-associated macrophages may be antitumoral. Interestingly, lower densities of various types of immunosuppressive cells are associated with decreased infiltration of effector T cells in distal and hilar cholangiocarcinoma, but not in intrahepatic cholangiocarcinoma. In intrahepatic cholangiocarcinoma, PD-L1+ tumor-associated macrophages exert their immunosuppressive function likely through promoting T cell exhaustion.This study suggests that the densities of Granzyme-B+CD8+ effector T cells and non-exhausted PD-1-EOMES-CD8+ T cells and the PD-L1 status in the tumor-associated macrophages are prognostic makers in cholangiocarcinomas. The study also supports targeting PD-L1+ tumor-associated macrophages as the immunotherapy for cholangiocarcinoma.© 2022. The Author(s).

基金：
This work was supported mainly by a MISP Grant from Merck (LZ). LZ is supported by an NIH Grant R01 CA169702, an NIH Grant R01 CA197296, an NIH SPORE Grant P50 CA062924, and an NIH Cancer Center Support Grant P30 CA006973.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2022]版：
大类 | 1 区 医学
小类 | 1 区 血液学 1 区 肿瘤学
最新[2023]版：
大类 | 1 区 医学
小类 | 1 区 血液学 1 区 肿瘤学
第一作者：
第一作者机构： [1]Department of Oncology, Johns Hopkins University School of Medicine,1650 Orleans Street, CRB1 Room 351, Baltimore, MD 21231, USA [2]Departmentof Surgery, Johns Hopkins University School of Medicine, Baltimore, MD,USA [3]The Sidney Kimmel Cancer Center, Johns Hopkins University Schoolof Medicine, Baltimore, MD, USA [4]The Bloomberg‑Kimmel Institute for CancerImmunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA
推荐引用方式(GB/T 7714)：
Xia Tao,Li Keyu,Niu Nan,et al.Immune cell atlas of cholangiocarcinomas reveals distinct tumor microenvironments and associated prognoses.[J].Journal of hematology & oncology.2022,15(1):37.doi:10.1186/s13045-022-01253-z.
APA：
Xia Tao,Li Keyu,Niu Nan,Shao Yingkuan,Ding Ding...&Zheng Lei.(2022).Immune cell atlas of cholangiocarcinomas reveals distinct tumor microenvironments and associated prognoses..Journal of hematology & oncology,15,(1)
MLA：
Xia Tao,et al."Immune cell atlas of cholangiocarcinomas reveals distinct tumor microenvironments and associated prognoses.".Journal of hematology & oncology 15..1(2022):37

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