HCA Data Explorer

Spatially organized multicellular immune hubs in human colorectal cancer

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Updated February 24, 2023

Immune responses to cancer are highly variable, with mismatch repair-deficient (MMRd) tumors exhibiting more anti-tumor immunity than mismatch repair-proficient (MMRp) tumors. To understand the rules governing these varied responses, we transcriptionally profiled 371,223 cells from colorectal tumors and adjacent normal tissues of 28 MMRp and 34 MMRd individuals. Analysis of 88 cell subsets and their 204 associated gene expression programs revealed extensive transcriptional and spatial remodeling across tumors. To discover hubs of interacting malignant and immune cells, we identified expression programs in different cell types that co-varied across tumors from affected individuals and used spatial profiling to localize coordinated programs. We discovered a myeloid cell-attracting hub at the tumor-luminal interface associated with tissue damage and an MMRd-enriched immune hub within the tumor, with activated T cells together with malignant and myeloid cells expressing T cell-attracting chemokines. By identifying interacting cellular programs, we reveal the logic underlying spatially organized immune-malignant cell networks.

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Karin Pelka1
Matan Hofree2
Jonathan H Chen3
Siranush Sarkizova4
Joshua D Pirl4
Vjola Jorgji5
Alborz Bejnood2
Danielle Dionne2
William H Ge4
Katherine H Xu6
Sherry X Chao7
Daniel R Zollinger8
David J Lieb4
Jason W Reeves8
Christopher A Fuhrman8
Margaret L Hoang8
Toni Delorey2
Lan T Nguyen2
Julia Waldman2
Max Klapholz9
Isaac Wakiro10
Ofir Cohen11
Julian Albers4
Christopher S Smillie2
Michael S Cuoco2
Jingyi Wu10
Mei-Ju Su10
Jason Yeung10
Brinda Vijaykumar12
Angela M Magnuson12
Natasha Asinovski12
Tabea Moll13
Max N Goder-Reiser13
Anise S Applebaum13
Lauren K Brais14
Laura K DelloStritto10
Sarah L Denning14
Susannah T Phillips13
Emma K Hill14
Julia K Meehan14
Dennie T Frederick13
Tatyana Sharova13
Abhay Kanodia10
Ellen Z Todres4
Judit Jané-Valbuena2
Moshe Biton15
Benjamin Izar16
Conner D Lambden9
Thomas E Clancy17
Ronald Bleday17
Nelya Melnitchouk17
Jennifer Irani17
Hiroko Kunitake18
David L Berger18
Amitabh Srivastava19
Jason L Hornick19
Shuji Ogino20
Asaf Rotem10
Sébastien Vigneau10
Bruce E Johnson21
Ryan B Corcoran22
Arlene H Sharpe23
Vijay K Kuchroo9
Kimmie Ng24
Marios Giannakis25
Linda T Nieman6
Genevieve M Boland26
Andrew J Aguirre25
Ana C Anderson27
Orit Rozenblatt-Rosen28
Aviv Regev29
Nir Hacohen30
1Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA; Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA.
2Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
3Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA; Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA; Department of Pathology, MGH, Boston, MA, USA.
4Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
5Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA; Department of Pathology, MGH, Boston, MA, USA.
6Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA.
7Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA; Department of Biomedical Informatics, HMS, Boston, MA, USA.
8NanoString Technologies Inc., Seattle, WA, USA.
9Evergrande Center for Immunologic Diseases, HMS and Brigham and Women's Hospital (BWH), Boston, MA, USA.
10Center for Cancer Genomics, Department of Medical Oncology, Dana-Farber Cancer Institute (DFCI), Boston, MA, USA.
11Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA; Center for Cancer Genomics, Department of Medical Oncology, Dana-Farber Cancer Institute (DFCI), Boston, MA, USA; Department of Medical Oncology, DFCI, Boston, MA, USA.
12Department of Immunology, HMS, Boston, MA, USA.
13Clinical Research Center, MGH, Boston, MA, USA.
14Clinical Research Center, DFCI, Boston, MA, USA.
15Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Molecular Biology, MGH, Boston, MA, USA.
16Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Center for Cancer Genomics, Department of Medical Oncology, Dana-Farber Cancer Institute (DFCI), Boston, MA, USA; Department of Medical Oncology, DFCI, Boston, MA, USA.
17Department of Surgery, BWH, Boston, MA, USA.
18Department of Surgery, MGH, Boston, MA, USA.
19Department of Pathology, BWH, Boston, MA, USA.
20Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA; Department of Pathology, BWH, Boston, MA, USA.
21Center for Cancer Genomics, Department of Medical Oncology, Dana-Farber Cancer Institute (DFCI), Boston, MA, USA; Department of Medical Oncology, DFCI, Boston, MA, USA.
22Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA; Department of Medicine, HMS, Boston, MA, USA.
23Evergrande Center for Immunologic Diseases, HMS and Brigham and Women's Hospital (BWH), Boston, MA, USA; Department of Immunology, Blavatnik Institute, HMS, Boston, MA, USA.
24Department of Medical Oncology, DFCI, Boston, MA, USA.
25Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA; Department of Medical Oncology, DFCI, Boston, MA, USA.
26Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA; Department of Surgery, MGH, Boston, MA, USA.
27Evergrande Center for Immunologic Diseases, HMS and Brigham and Women's Hospital (BWH), Boston, MA, USA. Electronic address: acanderson@bwh.harvard.edu.
28Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA. Electronic address: orit@broadinstitute.org.
29Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Howard Hughes Medical Institute and Koch Institute for Integrative Cancer Research, Department of Biology, MIT, Cambridge, MA, USA. Electronic address: aviv.regev.sc@gmail.com.
30Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA; Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA; Department of Immunology, HMS, Boston, MA, USA. Electronic address: nhacohen@mgh.harvard.edu.
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To reference this project, please use the following link:

https://explore.data.humancellatlas.org/projects/6f03e4ad-9305-4bfa-a5b6-929ffb1d94bd
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GEO Series Accessions:

Atlas

None

Analysis Portals

None

Project Label

MMRdandMMRpColorectalCancerAtlas

Species

Homo sapiens

Sample Type

specimens

Anatomical Entity

colon

Organ Part

7 organ parts

Selected Cell Types

Unspecified

Disease Status (Specimen)

2 disease statuses

Disease Status (Donor)

colorectal adenocarcinoma

Development Stage

human adult stage

Library Construction Method

2 library construction methods

Nucleic Acid Source

single cell

Paired End

false

Analysis Protocol

analysis_protocol_1, analysis_protocol_2

File Format

3 file formats

Cell Count Estimate

371.2k

Donor Count

62
csv.gz2 file(s)h51 file(s)xlsx1 file(s)