Immune suppressive landscape in the human esophageal squamous cell carcinoma microenvironment.
Immune suppressive landscape in the human esophageal squamous cell carcinoma microenvironment.
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人食管鳞状细胞癌微环境中的免疫抑制景观
DOI：
10.1038/s41467-020-20019-0
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发表时间：
2020-12-08
影响因子：
16.6
通讯作者：
Shen L
中科院分区：
文献类型：
--
作者：
Zheng Y;Chen Z;Han Y;Han L;Zou X;Zhou B;Hu R;Hao J;Bai S;Xiao H;Li WV;Bueker A;Ma Y;Xie G;Yang J;Chen S;Li H;Cao J;Shen L
癌症免疫疗法彻底改变了癌症治疗，它在很大程度上依赖于对肿瘤微环境（TME）免疫格局的全面了解。在这里，我们获得了一个详细的免疫细胞图谱食管鳞状细胞癌（ESCC）在单细胞分辨率。耗尽的T和NK细胞、调节性T细胞（TMF）、交替活化的巨噬细胞和致耐受性树突状细胞在TME中占主导地位。结合T细胞受体（TCR）测序的转录谱分析揭示了T细胞群体中的谱系连接。CD8 T细胞显示出从预耗尽到耗尽的T细胞的连续进展。虽然耗尽的CD4、CD8 T和NK细胞是TME中的主要增殖细胞组分，但巨噬细胞和TME之间的串扰有助于TME中的潜在免疫抑制。我们的研究结果表明，几种免疫抑制机制，可能是同时负责免疫监视失败。特异性靶向这些免疫抑制途径可能会重新激活ESCC中的抗肿瘤免疫应答。了解肿瘤微环境对于免疫疗法的疗效至关重要。在这里，作者描述了食管鳞状细胞癌的免疫景观，并提出了几种免疫抑制机制，这些机制在靶向后可能会恢复抗肿瘤免疫反应。
Cancer immunotherapy has revolutionized cancer treatment, and it relies heavily on the comprehensive understanding of the immune landscape of the tumor microenvironment (TME). Here, we obtain a detailed immune cell atlas of esophageal squamous cell carcinoma (ESCC) at single-cell resolution. Exhausted T and NK cells, regulatory T cells (Tregs), alternatively activated macrophages and tolerogenic dendritic cells are dominant in the TME. Transcriptional profiling coupled with T cell receptor (TCR) sequencing reveal lineage connections in T cell populations. CD8 T cells show continuous progression from pre-exhausted to exhausted T cells. While exhausted CD4, CD8 T and NK cells are major proliferative cell components in the TME, the crosstalk between macrophages and Tregs contributes to potential immunosuppression in the TME. Our results indicate several immunosuppressive mechanisms that may be simultaneously responsible for the failure of immuno-surveillance. Specific targeting of these immunosuppressive pathways may reactivate anti-tumor immune responses in ESCC. Understanding the tumour microenvironment is essential for the efficacy of immunotherapies. Here the authors describe the immune landscape in esophageal squamous cell carcinoma and suggest several immunosuppressive mechanisms, which upon targeting may restore anti-tumour immune response.
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影响因子：
64.8
作者：
Cancer Genome Atlas Research Network;Analysis Working Group: Asan University;BC Cancer Agency;Brigham and Women’s Hospital;Broad Institute;Brown University;Case Western Reserve University;Dana-Farber Cancer Institute;Duke University;Greater Poland Cancer Centre;Harvard Medical School;Institute for Systems Biology;KU Leuven;Mayo Clinic;Memorial Sloan Kettering Cancer Center;National Cancer Institute;Nationwide Children’s Hospital;Stanford University;University of Alabama;University of Michigan;University of North Carolina;University of Pittsburgh;University of Rochester;University of Southern California;University of Texas MD Anderson Cancer Center;University of Washington;Van Andel Research Institute;Vanderbilt University;Washington University;Genome Sequencing Center: Broad Institute;Washington University in St. Louis;Genome Characterization Centers: BC Cancer Agency;Broad Institute;Harvard Medical School;Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University;University of North Carolina;University of Southern California Epigenome Center;University of Texas MD Anderson Cancer Center;Van Andel Research Institute;Genome Data Analysis Centers: Broad Institute;Brown University:;Harvard Medical School;Institute for Systems Biology;Memorial Sloan Kettering Cancer Center;University of California Santa Cruz;University of Texas MD Anderson Cancer Center;Biospecimen Core Resource: International Genomics Consortium;Research Institute at Nationwide Children’s Hospital;Tissue Source Sites: Analytic Biologic Services;Asan Medical Center;Asterand Bioscience;Barretos Cancer Hospital;BioreclamationIVT;Botkin Municipal Clinic;Chonnam National University Medical School;Christiana Care Health System;Cureline;Duke University;Emory University;Erasmus University;Indiana University School of Medicine;Institute of Oncology of Moldova;International Genomics Consortium;Invidumed;Israelitisches Krankenhaus Hamburg;Keimyung University School of Medicine;Memorial Sloan Kettering Cancer Center;National Cancer Center Goyang;Ontario Tumour Bank;Peter MacCallum Cancer Centre;Pusan National University Medical School;Ribeirão Preto Medical School;St. Joseph’s Hospital &Medical Center;St. Petersburg Academic University;Tayside Tissue Bank;University of Dundee;University of Kansas Medical Center;University of Michigan;University of North Carolina at Chapel Hill;University of Pittsburgh School of Medicine;University of Texas MD Anderson Cancer Center;Disease Working Group: Duke University;Memorial Sloan Kettering Cancer Center;National Cancer Institute;University of Texas MD Anderson Cancer Center;Yonsei University College of Medicine;Data Coordination Center: CSRA Inc.;Project Team: National Institutes of Health
通讯作者：
Project Team: National Institutes of Health
DOI：
10.1073/pnas.1619863114
发表时间：
2017-04-11
影响因子：
11.1
作者：
Briseno, Carlos G.;Gargaro, Marco;Murphy, Kenneth M.
通讯作者：
Murphy, Kenneth M.
从头表观遗传程序抑制PD-1封锁介导的T细胞再生。
影响因子：
64.5
作者：
Ghoneim HE;Fan Y;Moustaki A;Abdelsamed HA;Dash P;Dogra P;Carter R;Awad W;Neale G;Thomas PG;Youngblood B
通讯作者：
Youngblood B
影响因子：
64.5
作者：
André P;Denis C;Soulas C;Bourbon-Caillet C;Lopez J;Arnoux T;Bléry M;Bonnafous C;Gauthier L;Morel A;Rossi B;Remark R;Breso V;Bonnet E;Habif G;Guia S;Lalanne AI;Hoffmann C;Lantz O;Fayette J;Boyer-Chammard A;Zerbib R;Dodion P;Ghadially H;Jure-Kunkel M;Morel Y;Herbst R;Narni-Mancinelli E;Cohen RB;Vivier E
通讯作者：
Vivier E
影响因子：
51.1
作者：
Kato, Ken;Cho, Byoung Chul;Kitagawa, Yuko
通讯作者：
Kitagawa, Yuko