Spatially organized multicellular immune hubs in human colorectal cancer
Name
1-s2.0-S0092867421009454-main.pdf
Description
Published version
Size
15.01 MB
Format
Adobe PDF
Checksum (MD5)
8cb8b15df14002b71febfecec7472f11
Author(s)
Regev, Aviv
Date Issued
2021
Journal
Cell
Publisher
Elsevier BV
Citation
Regev, Aviv. 2021. "Spatially organized multicellular immune hubs in human colorectal cancer." Cell, 184 (18).
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/J.CELL.2021.08.003
