Spatially organized multicellular immune hubs in human colorectal cancer 

 

Summary

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.

 

 

Interactive exploration with the single-cell portal:

The single-cell portal allows for interactive exploration of gene expression from this study. See the help section or the following article for instructions on how to get started.

PartitionCells Tumor/NormalDescription 
Global view258,359/112,864All cells post quality control filtering.
Epithelial cells113,593/55,079Epithelial cells.
Immune cells135,140/51,954All Immune cells. 
T/NK/ILC cells61,254/15,933T, NK, ILC cell types. 
B cells13,560/12,117 B cells. 
Plasma cells17,975/19,848 Plasma cells. 
Mast cells2,53/1,119  Mast cells. 
Myeloid cells39,598/2,947 Myeloid cells. 
Stromal cells9,626/5,831  All stromal cell types (e.g., fibroblast, endothelial, pericytes, etc.)

 

 

Additional supplemental data:

 

Companion website describing expression programs

The website includes basic information for all cell-type specific expression programs identified in this cohort using consensus non-negative matrix factorization (ccNMF). 

 

Interactive offline data exploration (using custom 10x loupe files):

Usage: Each zipped folder contains a 10x .cloupe file which can be used for offline interactive exploration of the data.  To open these files please follow the instructions here to download and install the latest version of the 10x single cell loupe cell browser.

 

Supplemental cell quality information

 

Supplemental software:

 

Additional online data:

  • Raw count data may also be downloaded from GEO: GSE178341
  • Due to patient privacy concerns, raw data access requires approval through dbGaP.
  • The NIH HTAN data portal also stores the data for this study: https://data.humantumoratlas.org

 

 

Imaging information

 

HALO Imaging features and kmeans cluster assignments:

HALO imaging feature file from patient specimen C132 

HALO imaging feature file from patient specimen C123

HALO imaging feature file from patient specimen C110

HALO imaging feature file from patient specimen C144

HALO imaging feature file from patient specimen C139

HALO imaging feature file from patient specimen C107

HALO imaging feature file from patient specimen C126

HALO imaging feature file from patient specimen C112

HALO imaging feature file from patient specimen C103

 

Last updated: Aug. 26th, 2021