An Immune Atlas of Clear Cell Renal Cell Carcinoma

被引:870
作者
Chevrier, Stephane [1 ]
Levine, Jacob Harrison [2 ]
Zanotelli, Vito Riccardo Tomaso [1 ,3 ,4 ]
Silina, Karina [5 ]
Schulz, Daniel [1 ]
Bacac, Marina [6 ]
Ries, Carola Hermine [7 ]
Ailles, Laurie [8 ,9 ]
Jewett, Michael Alexander Spencer [9 ]
Moch, Holger [10 ]
van den Broek, Maries [5 ]
Beisel, Christian [11 ]
Stadler, Michael Beda [12 ,13 ]
Gedye, Craig [14 ]
Reis, Bernhard [15 ]
Pe'er, Dana [2 ]
Bodenmiller, Bernd [1 ]
机构
[1] Univ Zurich, Inst Mol Life Sci, Winterthurerstr 190, CH-8057 Zurich, Switzerland
[2] Sloan Kettering Inst, Computat & Syst Biol Program, 1275 York Ave, New York, NY 10065 USA
[3] ETH, Syst Biol PhD Program, Life Sci Zurich Grad Sch, CH-8057 Zurich, Switzerland
[4] Univ Zurich, CH-8057 Zurich, Switzerland
[5] Univ Zurich, Inst Expt Immunol, Winterthurerstr 190, CH-8057 Zurich, Switzerland
[6] Roche Innovat Ctr Zurich, Roche Pharma Res & Early Dev, Wagistr 18, CH-8952 Schlieren, Switzerland
[7] Roche Innovat Ctr Zurich, Roche Pharma Res & Early Dev, Nonnenwald 2, D-82377 Penzberg, Germany
[8] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 1L7, Canada
[9] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON M5G 1L7, Canada
[10] Univ Hosp Zurich, Inst Surg Pathol, Schmelzbergstr 12, CH-8091 Zurich, Switzerland
[11] ETH, Dept Biosyst Sci & Engn, Mattenstr 26, CH-4058 Basel, Switzerland
[12] Friedrich Miescher Inst Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland
[13] Swiss Inst Bioinformat, Mattenstr 26, CH-4058 Basel, Switzerland
[14] Univ Newcastle, Hunter Med Res Inst, Sch Biomed Sci & Pharm, Newcastle, NSW 2035, Australia
[15] Roche Innovat Ctr Basel, Pharmaceut Sci, Roche Pharma Res & Early Dev, Grenzacherstr 124, CH-4070 Basel, Switzerland
基金
欧洲研究理事会; 澳大利亚国家健康与医学研究理事会; 瑞士国家科学基金会;
关键词
TUMOR-ASSOCIATED MACROPHAGES; T-CELLS; GLIOMA PROGRESSION; CANCER; POLARIZATION; EXPRESSION; ACTIVATION; REVEALS; CD38; MECHANISMS;
D O I
10.1016/j.cell.2017.04.016
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Immune cells in the tumor microenvironment modulate cancer progression and are attractive therapeutic targets. Macrophages and T cells are key components of the microenvironment, yet their phenotypes and relationships in this ecosystem and to clinical outcomes are ill defined. We used mass cytometry with extensive antibody panels to perform in-depth immune profiling of samples from 73 clear cell renal cell carcinoma (ccRCC) patients and five healthy controls. In 3.5 million measured cells, we identified 17 tumor-associated macrophage phenotypes, 22 T cell phenotypes, and a distinct immune composition correlated with progression-free survival, thereby presenting an in-depth human atlas of the immune tumor microenvironment in this disease. This study revealed potential biomarkers and targets for immunotherapy development and validated tools that can be used for immune profiling of other tumor types.
引用
收藏
页码:736 / 749
页数:14
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