A Single-Cell Atlas of the Tumor and Immune Ecosystem of Human Breast Cancer

被引：587

作者：

Wagner, Johanna ^{[1
,2
,3
,17
]}

Rapsomaniki, Maria Anna ^{[4
]}

Chevrier, Stephane ^{[1
,17
]}

Anzeneder, Tobias ^{[5
]}

Langwieder, Claus ^{[6
]}

Dykgers, August ^{[6
]}

Rees, Martin ^{[6
]}

Ramaswamy, Annette ^{[7
]}

Muenst, Simone ^{[8
,9
]}

Soysa, Savas Deniz ^{[10
,11
,12
]}

Jacobs, Andrea ^{[1
,17
]}

Windhager, Jonas ^{[1
,3
,13
,17
]}

Silina, Karina ^{[14
]}

van den Broek, Manes ^{[14
]}

Dedes, Konstantin Johannes ^{[15
]}

Martinez, Maria Rodriguez ^{[4
]}

Weber, Walter Paul ^{[11
,12
,16
]}

Bodenmiller, Bernd ^{[1
,17
]}

机构：

[1] Univ Zurich, Inst Mol Life Sci, Winterthurerstr 190, CH-8057 Zurich, Switzerland

[2] Swiss Fed Inst Technol, Life Sci Zurich Grad Sch, Mol Life Sci PhD Program, Winterthurerstr 190, CH-8057 Zurich, Switzerland

[3] Univ Zurich, Winterthurerstr 190, CH-8057 Zurich, Switzerland

[4] IBM Res Zurich, Saeumerstr 4, CH-8803 Ruschlikon, Switzerland

[5] Patients Tumor Bank Hope PATH Biobank, PO 750729, D-81337 Munich, Germany

[6] Inst Pathol Josefshaus, Amalienstr 21, D-44137 Dortmund, Germany

[7] Univ Hosp Giessen & Marburg, Inst Pathol, Baldingerstr, D-35043 Marburg, Germany

[8] Univ Hosp Basel, Inst Pathol, Schoenbeinstr 40, CH-4031 Basel, Switzerland

[9] Univ Basel, Schoenbeinstr 40, CH-4031 Basel, Switzerland

[10] Univ Hosp Basel, Clarunis, Spitalstr 21, CH-4031 Basel, Switzerland

[11] Univ Basel, Spitalstr 21, CH-4031 Basel, Switzerland

[12] Univ Hosp Basel, Breast Canc Ctr, Spitalstr 21, CH-4031 Basel, Switzerland

[13] Swiss Fed Inst Technol, Life Sci Zurich Grad Sch, Syst Biol PhD Program, Winterthurerstr 190, CH-8057 Zurich, Switzerland

[14] Univ Zurich, Inst Expt Immunol, Winterthurerstr 190, CH-8057 Zurich, Switzerland

[15] Univ Hosp Zurich, Breast Canc Ctr, Frauenklinikstr 10, CH-8091 Zurich, Switzerland

[16] Univ Hosp Basel, Dept Surg, Spitalstr 21, CH-4031 Basel, Switzerland

[17] Univ Zurich, Dept Quantitat Biomed, Winterthurerstr 190, CH-8057 Zurich, Switzerland

来源：

CELL | 2019年 / 177卷 / 05期

基金：

欧洲研究理事会;

关键词：

MASS CYTOMETRY; HETEROGENEITY; MANAGEMENT; RESISTANCE; THERAPY; REVEALS; IMPACT; HER2;

D O I：

10.1016/j.cell.2019.03.005

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Breast cancer is a heterogeneous disease. Tumor cells and associated healthy cells form ecosystems that determine disease progression and response to therapy. To characterize features of breast cancer ecosystems and their associations with clinical data, we analyzed 144 human breast tumor and 50 non-tumor tissue samples using mass cytometry. The expression of 73 proteins in 26 million cells was evaluated using tumor and immune cell-centric antibody panels. Tumors displayed individuality in tumor cell composition, including phenotypic abnormalities and phenotype dominance. Relationship analyses between tumor and immune cells revealed characteristics of ecosystems related to immunosuppression and poor prognosis. High frequencies of PD-L1(+) tumor-associated macrophages and exhausted T cells were found in high-grade ER+ and ER- tumors. This largo-scale, single-cell atlas deepens our understanding breast tumor ecosystems and suggests that ecosystem-based patient classification will facilitate identification of individuals for precision medicine approaches targeting the tumor and its immunoenvironment.

引用

页码：1330 / +

页数：34

共 68 条

[1]

Amin MB, 2017, Ajcc cancer staging manual, V8th

[2] Multiplexed ion beam imaging of human breast tumors [J].

Angelo, Michael ;

Bendall, Sean C. ;

Finck, Rachel ;

Hale, Matthew B. ;

Hitzman, Chuck ;

Borowsky, Alexander D. ;

Levenson, Richard M. ;

Lowe, John B. ;

Liu, Scot D. ;

Zhao, Shuchun ;

Natkunam, Yasodha ;

Nolan, Garry P. .

NATURE MEDICINE, 2014, 20 (04) :436-+

[3] Single-Cell Map of Diverse Immune Phenotypes in the Breast Tumor Microenvironment [J].

Azizi, Elham ;

Carr, Ambrose J. ;

Plitas, George ;

Cornish, Andrew E. ;

Konopacki, Catherine ;

Prabhakaran, Sandhya ;

Nainys, Juozas ;

Wu, Kenmin ;

Kiseliovas, Vaidotas ;

Setty, Manu ;

Choi, Kristy ;

Fromme, Rachel M. ;

Phuong Dao ;

McKenney, Peter T. ;

Wasti, Ruby C. ;

Kadaveru, Krishna ;

Mazutis, Linas ;

Rudensky, Alexander Y. ;

Pe'er, Dana .

CELL, 2018, 174 (05) :1293-+

[4] Mass Cytometry: Technique for Real Time Single Cell Multitarget Immunoassay Based on Inductively Coupled Plasma Time-of-Flight Mass Spectrometry [J].

Bandura, Dmitry R. ;

Baranov, Vladimir I. ;

Ornatsky, Olga I. ;

Antonov, Alexei ;

Kinach, Robert ;

Lou, Xudong ;

Pavlov, Serguei ;

Vorobiev, Sergey ;

Dick, John E. ;

Tanner, Scott D. .

ANALYTICAL CHEMISTRY, 2009, 81 (16) :6813-6822

[5] Single-Cell Mass Cytometry of Differential Immune and Drug Responses Across a Human Hematopoietic Continuum [J].

Bendall, Sean C. ;

Simonds, Erin F. ;

Qiu, Peng ;

Amir, El-ad D. ;

Krutzik, Peter O. ;

Finck, Rachel ;

Bruggner, Robert V. ;

Melamed, Rachel ;

Trejo, Angelica ;

Ornatsky, Olga I. ;

Balderas, Robert S. ;

Plevritis, Sylvia K. ;

Sachs, Karen ;

Pe'er, Dana ;

Tanner, Scott D. ;

Nolan, Garry P. .

SCIENCE, 2011, 332 (6030) :687-696

[6] Random forests [J].

Breiman, L .

MACHINE LEARNING, 2001, 45 (01) :5-32

[7] Tumor-infiltrating lymphocyte composition, organization and PD-1/PD-L1 expression are linked in breast cancer [J].

Buisseret, Laurence ;

Garaud, Soizic ;

de Wind, Alexandre ;

Van den Eynden, Gert ;

Boisson, Anais ;

Solinas, Cinzia ;

Gu-Trantien, Chunyan ;

Naveaux, Celine ;

Lodewyckx, Jean-Nicolas ;

Duvillier, Hugues ;

Craciun, Ligia ;

Veys, Isabelle ;

Larsimont, Denis ;

Piccart-Gebhart, Martine ;

Stagg, John ;

Sotiriou, Christos ;

Willard-Gallo, Karen .

ONCOIMMUNOLOGY, 2017, 6 (01)

[8] Targeting macrophages: therapeutic approaches in cancer [J].

Cassetta, Luca ;

Pollard, Jeffrey W. .

NATURE REVIEWS DRUG DISCOVERY, 2018, 17 (12) :887-904

[9] AirLab: a cloud-based platform to manage and share antibody-based single-cell research [J].

Catena, Raul ;

Ozcan, Alaz ;

Jacobs, Andrea ;

Chevrier, Stephane ;

Bodenmiller, Bernd .

GENOME BIOLOGY, 2016, 17

[10] Obesity reversibly depletes the basal cell population and enhances mammary epithelial cell estrogen receptor alpha expression and progenitor activity [J].

Chamberlin, Tamara ;

D'Amato, Joseph V. ;

Arendt, Lisa M. .

BREAST CANCER RESEARCH, 2017, 19

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