Spatially organized multicellular immune hubs in human colorectal cancer
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 patients. 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 patient tumors 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 thus reveal the logic underlying spatially organized immune-malignant cell networks.
Single cell portal for interactive data exploration
Data from this single cell cohort may be interactively explored using the Broad Institute’s single cell portal.
Supplemental annotations of consensus NMF gene programs
- T/NK/ILC cells
- B cells
- Plasma cells
- Mast cells
- Myloid cells
- Stromal cells
- Epithelial cells
- MMRd epithelial tumor cells
- MMRp epithelial tumor cells
Interactive offline data exploration (using custom 10x loupe files):
Supplemental software:
- [Principle analysis code used in the study] ()
- UMI saturation QC analysis – pending release (check back Sept. 9th)
- Terra/Fireclouad workflows:
Supplemental online data
- Raw count data may also be downloaded from GEO: GSE178341
- Due to patient privacy concerns, raw data access requires approval through dbGaP.