Tumour evolution and microenvironment interactions in 2D and 3D space

Chia-Kuei Mo, Jingxian Liu, Siqi Chen, Erik Storrs, Andre Luiz N. Targino da Costa, Andrew Houston, Michael C. Wendl, Reyka G. Jayasinghe, Michael D. Iglesia, Cong Ma, John M. Herndon, Austin N. Southard-Smith, Xinhao Liu, Jacqueline Mudd, Alla Karpova, Andrew Shinkle, S. Peter Goedegebuure, Abdurrahman Taha Mousa Ali Abdelzaher, Peng Bo, Lauren Fulghum, Samantha Livingston, Metin Balaban, Angela Hill, Joseph E. Ippolito, Vesteinn Thorsson, Jason M. Held, Ian S. Hagemann, Eric H. Kim, Peter O. Bayguinov, Albert H. Kim, Mary M. Mullen, Kooresh I. Shoghi, Tao Ju, Melissa A. Reimers, Cody Weimholt, Liang-I Kang, Sidharth V. Puram, Deborah J. Veis, Russell Pachynski, Katherine C. Fuh, Milan G. Chheda, William E. Gillanders (), Ryan C. Fields (), Benjamin J. Raphael (), Feng Chen () and Li Ding ()
Additional contact information
Chia-Kuei Mo: Washington University in St Louis
Jingxian Liu: Washington University in St Louis
Siqi Chen: Washington University in St Louis
Erik Storrs: Washington University in St Louis
Andre Luiz N. Targino da Costa: Washington University in St Louis
Andrew Houston: Washington University in St Louis
Michael C. Wendl: Washington University in St Louis
Reyka G. Jayasinghe: Washington University in St Louis
Michael D. Iglesia: Washington University in St Louis
Cong Ma: Princeton University
John M. Herndon: Washington University in St Louis
Austin N. Southard-Smith: Washington University in St Louis
Xinhao Liu: Princeton University
Jacqueline Mudd: Washington University in St Louis
Alla Karpova: Washington University in St Louis
Andrew Shinkle: Washington University in St Louis
S. Peter Goedegebuure: Washington University in St Louis
Abdurrahman Taha Mousa Ali Abdelzaher: Washington University in St Louis
Peng Bo: Washington University in St Louis
Lauren Fulghum: Washington University in St Louis
Samantha Livingston: Washington University in St Louis
Metin Balaban: Princeton University
Angela Hill: Washington University in St Louis
Joseph E. Ippolito: Washington University in St Louis
Vesteinn Thorsson: Institute for Systems Biology
Jason M. Held: Washington University in St Louis
Ian S. Hagemann: Washington University in St Louis
Eric H. Kim: Washington University
Peter O. Bayguinov: Washington University School of Medicine
Albert H. Kim: Washington University in St Louis
Mary M. Mullen: Washington University
Kooresh I. Shoghi: Washington University in St Louis
Tao Ju: Washington University in St Louis
Melissa A. Reimers: Washington University School of Medicine
Cody Weimholt: Washington University in St Louis
Liang-I Kang: Washington University in St Louis
Sidharth V. Puram: Washington University in St Louis
Deborah J. Veis: Washington University in St Louis
Russell Pachynski: Washington University in St Louis
Katherine C. Fuh: Washington University in St Louis
Milan G. Chheda: Washington University in St Louis
William E. Gillanders: Washington University in St Louis
Ryan C. Fields: Washington University in St Louis
Benjamin J. Raphael: Princeton University
Feng Chen: Washington University in St Louis
Li Ding: Washington University in St Louis

Nature, 2024, vol. 634, issue 8036, 1178-1186

Abstract: Abstract To study the spatial interactions among cancer and non-cancer cells1, we here examined a cohort of 131 tumour sections from 78 cases across 6 cancer types by Visium spatial transcriptomics (ST). This was combined with 48 matched single-nucleus RNA sequencing samples and 22 matched co-detection by indexing (CODEX) samples. To describe tumour structures and habitats, we defined ‘tumour microregions’ as spatially distinct cancer cell clusters separated by stromal components. They varied in size and density among cancer types, with the largest microregions observed in metastatic samples. We further grouped microregions with shared genetic alterations into ‘spatial subclones’. Thirty five tumour sections exhibited subclonal structures. Spatial subclones with distinct copy number variations and mutations displayed differential oncogenic activities. We identified increased metabolic activity at the centre and increased antigen presentation along the leading edges of microregions. We also observed variable T cell infiltrations within microregions and macrophages predominantly residing at tumour boundaries. We reconstructed 3D tumour structures by co-registering 48 serial ST sections from 16 samples, which provided insights into the spatial organization and heterogeneity of tumours. Additionally, using an unsupervised deep-learning algorithm and integrating ST and CODEX data, we identified both immune hot and cold neighbourhoods and enhanced immune exhaustion markers surrounding the 3D subclones. These findings contribute to the understanding of spatial tumour evolution through interactions with the local microenvironment in 2D and 3D space, providing valuable insights into tumour biology.

Date: 2024
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-024-08087-4 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:634:y:2024:i:8036:d:10.1038_s41586-024-08087-4

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-024-08087-4

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().