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

Laura Kuett(University of Zurich), Raúl Catena(University of Zurich), Alaz Özcan(University of Zurich), Alex Plüss(University of Zurich), H. Raza Ali(University of Cambridge), M. Al Sa’d(University of Cambridge), Shahar Alon(McGovern Institute for Brain Research), Samuel Aparício(University of British Columbia), Giorgia Battistoni(University of Cambridge), Shankar Balasubramanian(University of Cambridge), Robert Becker, Bernd Bodenmiller(ETH Zurich), E. S. Boyden(McGovern Institute for Brain Research), Dario Bressan(University of Cambridge), Alejandra Bruna(University of Cambridge), Marcel Burger(ETH Zurich), Carlos Caldas(University of Cambridge), Maurizio Callari(University of Cambridge), Ian G. Cannell(University of Cambridge), Helen Casbolt(University of Cambridge), N. Chornay(University of Cambridge), Y. Cui(McGovern Institute for Brain Research), A. Dariush(University of Cambridge), K. Dinh(Ludwig Cancer Research), A. Emenari(McGovern Institute for Brain Research), Y. Eyal-Lubling(University of Cambridge), Joy Linyue Fan(Howard Hughes Medical Institute), Ali Fatemi(University of Cambridge), Edward A. Fisher(University of Cambridge), E. A. González-Solares(University of Cambridge), C. Gónzalez-Fernández(University of Cambridge), Daniel Goodwin(McGovern Institute for Brain Research), Wendy Greenwood(University of Cambridge), Francesco Grimaldi, Gregory J. Hannon(University of Cambridge), Shelley Harris, Cristina Jauset(University of Cambridge), Johanna A. Joyce(Ludwig Cancer Research), Emmanouil D. Karagiannis(McGovern Institute for Brain Research), Tatjana Kovačević(University of Cambridge), Laura Kuett(University of Zurich), Russell Kunes(Ludwig Cancer Research), A. Yoldaş(University of Cambridge), Daniel Lai(University of British Columbia), Emma Laks(University of British Columbia), H. Lee(Howard Hughes Medical Institute), M. Lee(University of Cambridge), Giulia Lerda(University of Cambridge), Y. Li(Provincial Health Services Authority), Andrew McPherson(Memorial Sloan Kettering Cancer Center), Neal L. Millar(University of Cambridge), Claire M. Mulvey(University of Cambridge), I. Nugent(University of Cambridge), Ciara H. O’Flanagan(Provincial Health Services Authority), Marta Pàez‐Ribes(University of Cambridge), I. Pearsall(University of Cambridge), Fatime Qosaj(University of Cambridge), Andrew Roth(University of British Columbia), Oscar M. Rueda(University of Cambridge), Tamara Ruiz(Provincial Health Services Authority), Kirsty Sawicka(University of Cambridge), Leonardo A. Sepúlveda(Howard Hughes Medical Institute), Sohrab P. Shah(Memorial Sloan Kettering Cancer Center), Abigail Shea(University of Cambridge), Anubhav Sinha(McGovern Institute for Brain Research), Adrian L. Smith(Provincial Health Services Authority), S. Tavaré(University of Cambridge), Sandra Tietscher(ETH Zurich), Ignacio Vázquez-Garćıa(Memorial Sloan Kettering Cancer Center), Siegfried Vogl, N. A. Walton(University of Cambridge), Asmamaw T. Wassie(McGovern Institute for Brain Research), Spencer S. Watson(Ludwig Cancer Research), Joanna Weselak, Sonja Wild(University of Cambridge), Elyse T. Williams(University of Cambridge), Jonas Windhager(ETH Zurich), C. Xia(Howard Hughes Medical Institute), Ping Zheng(Howard Hughes Medical Institute), Xiaowei Zhuang(Howard Hughes Medical Institute), Peter Schraml(University Hospital of Zurich), Holger Moch(University Hospital of Zurich), Natalie de Souza(University of Zurich), Bernd Bodenmiller(ETH Zurich)
Nature Cancer
December 24, 2021
10.1038/s43018-021-00301-w
Cited by 214Open Access
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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.

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