Three-dimensional imaging mass cytometry for highly multiplexed molecular and cellular mapping of tissues and the tumor microenvironment

Cancer Grand Challenges IMAXT Consortium

doi:10.1038/s43018-021-00301-w

Three-dimensional imaging mass cytometry for highly multiplexed molecular and cellular mapping of tissues and the tumor microenvironment

Cancer Grand Challenges IMAXT Consortium

Research output: Contribution to journal › Article › peer-review

166 Scopus citations

Abstract

A holistic understanding of tissue and organ structure and function requires the detection of molecular constituents in their original three-dimensional (3D) context. Imaging mass cytometry (IMC) enables simultaneous detection of up to 40 antigens and transcripts using metal-tagged antibodies but has so far been restricted to two-dimensional imaging. Here we report the development of 3D IMC for multiplexed 3D tissue analysis at single-cell resolution and demonstrate the utility of the technology by analysis of human breast cancer samples. The resulting 3D models reveal cellular and microenvironmental heterogeneity and cell-level tissue organization not detectable in two dimensions. 3D IMC will prove powerful in the study of phenomena occurring in 3D space such as tumor cell invasion and is expected to provide invaluable insights into cellular microenvironments and tissue architecture.

Original language	English
Pages (from-to)	122-133
Number of pages	12
Journal	Nature Cancer
Volume	3
Issue number	1
DOIs	https://doi.org/10.1038/s43018-021-00301-w
State	Published - Jan 2022
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2021, The Author(s).

Funding

We thank S. Engler and A. Jacobs (University of Zurich), A. B. Sobottka-Brillout and S. Dettwiler (Institute of Pathology and Molecular Pathology, University Hospital Zurich) and F. Prutek (Tissue Biobank, University Hospital Zurich) for technical support. We thank R. A. Wepf (University of Queensland), H. Gnaegi (Diatome AG) and U. Ziegler, A. Käch and G. Barmettler (University of Zurich) for their invaluable guidance with the paraffin ultramicrotomy procedure. We also thank J. Windhager and V. Zanotelli for their advice on computational analysis. L.K. is supported by a Cancer Research UK Grand Challenge grant. The work of B.B. was supported by the Swiss National Science Foundation R’Equip grant 316030-139220, an SNSF Assistant Professorship grant PP00P3-144874, the European Research Council (ERC) grant under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC grant no. 336921 and under the European Union’s Horizon 2020 Program ERC Consolidator grant no. 866074, the Cancer Research UK IMAXT Grand Challenge grant and a National Institutes of Health HubMAP grant.

Funders	Funder number
Cancer Research UK IMAXT
European Union’s Horizon 2020 Program ERC	866074
National Institutes of Health
National Cancer Institute	P30CA008748
Seventh Framework Programme	FP/2007-2013, 336921
Cancer Research UK
European Commission
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung	316030-139220, PP00P3-144874

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s43018-021-00301-w

Cite this

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title = "Three-dimensional imaging mass cytometry for highly multiplexed molecular and cellular mapping of tissues and the tumor microenvironment",

abstract = "A holistic understanding of tissue and organ structure and function requires the detection of molecular constituents in their original three-dimensional (3D) context. Imaging mass cytometry (IMC) enables simultaneous detection of up to 40 antigens and transcripts using metal-tagged antibodies but has so far been restricted to two-dimensional imaging. Here we report the development of 3D IMC for multiplexed 3D tissue analysis at single-cell resolution and demonstrate the utility of the technology by analysis of human breast cancer samples. The resulting 3D models reveal cellular and microenvironmental heterogeneity and cell-level tissue organization not detectable in two dimensions. 3D IMC will prove powerful in the study of phenomena occurring in 3D space such as tumor cell invasion and is expected to provide invaluable insights into cellular microenvironments and tissue architecture.",

author = "\{Cancer Grand Challenges IMAXT Consortium\} and Laura Kuett and Ra{\'u}l Catena and Alaz {\"O}zcan and Alex Pl{\"u}ss and Ali, \{H. R.\} and Sa{\textquoteright}d, \{M. Al\} and S. Alon and S. Aparicio and G. Battistoni and S. Balasubramanian and R. Becker and B. Bodenmiller and Boyden, \{E. S.\} and D. Bressan and A. Bruna and Marcel Burger and C. Caldas and M. Callari and Cannell, \{I. G.\} and H. Casbolt and N. Chornay and Y. Cui and A. Dariush and K. Dinh and A. Emenari and Y. Eyal-Lubling and J. Fan and A. Fatemi and E. Fisher and Gonz{\'a}lez-Solares, \{E. A.\} and C. Gonz{\'a}lez-Fern{\'a}ndez and D. Goodwin and W. Greenwood and F. Grimaldi and Hannon, \{G. J.\} and S. Harris and C. Jauset and Joyce, \{J. A.\} and Karagiannis, \{E. D.\} and T. Kova{\v c}evi{\'c} and L. Kuett and R. Kunes and Yolda{\c s}, \{A. K{\"u}pc{\"u}\} and D. Lai and E. Laks and H. Lee and M. Lee and G. Lerda and Y. Li and A. McPherson",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2022",

month = jan,

doi = "10.1038/s43018-021-00301-w",

language = "אנגלית",

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AU - Kuett, Laura

AU - Catena, Raúl

AU - Özcan, Alaz

AU - Plüss, Alex

AU - Ali, H. R.

AU - Sa’d, M. Al

AU - Alon, S.

AU - Aparicio, S.

AU - Battistoni, G.

AU - Balasubramanian, S.

AU - Becker, R.

AU - Bodenmiller, B.

AU - Boyden, E. S.

AU - Bressan, D.

AU - Bruna, A.

AU - Burger, Marcel

AU - Caldas, C.

AU - Callari, M.

AU - Cannell, I. G.

AU - Casbolt, H.

AU - Chornay, N.

AU - Cui, Y.

AU - Dariush, A.

AU - Dinh, K.

AU - Emenari, A.

AU - Eyal-Lubling, Y.

AU - Fan, J.

AU - Fatemi, A.

AU - Fisher, E.

AU - González-Solares, E. A.

AU - González-Fernández, C.

AU - Goodwin, D.

AU - Greenwood, W.

AU - Grimaldi, F.

AU - Hannon, G. J.

AU - Harris, S.

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AU - Joyce, J. A.

AU - Karagiannis, E. D.

AU - Kovačević, T.

AU - Kuett, L.

AU - Kunes, R.

AU - Yoldaş, A. Küpcü

AU - Lai, D.

AU - Laks, E.

AU - Lee, H.

AU - Lee, M.

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AU - Li, Y.

AU - McPherson, A.

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AB - A holistic understanding of tissue and organ structure and function requires the detection of molecular constituents in their original three-dimensional (3D) context. Imaging mass cytometry (IMC) enables simultaneous detection of up to 40 antigens and transcripts using metal-tagged antibodies but has so far been restricted to two-dimensional imaging. Here we report the development of 3D IMC for multiplexed 3D tissue analysis at single-cell resolution and demonstrate the utility of the technology by analysis of human breast cancer samples. The resulting 3D models reveal cellular and microenvironmental heterogeneity and cell-level tissue organization not detectable in two dimensions. 3D IMC will prove powerful in the study of phenomena occurring in 3D space such as tumor cell invasion and is expected to provide invaluable insights into cellular microenvironments and tissue architecture.

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AN - SCOPUS:85121729156

SN - 2662-1347

VL - 3

SP - 122

EP - 133

JO - Nature Cancer

JF - Nature Cancer

IS - 1

ER -

Three-dimensional imaging mass cytometry for highly multiplexed molecular and cellular mapping of tissues and the tumor microenvironment

Abstract

Bibliographical note

Funding

UN SDGs

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