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.
DNA copy-number alterations underlie gene expression differences between microsatellite stable and unstable colorectal cancers.
Diagnosis of ulcerative colitis before onset of inflammation by multivariate modeling of genome-wide gene expression data
The tumor-promoting actions of TNF-alpha involve TNFR1 and IL-17 in ovarian cancer in mice and humans.
Unique ectopic lymph node-like structures present in human primary colorectal carcinoma are identified by immune gene array profiling.
Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett's epithelium
Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape.
Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value
Aberrant epithelial GREM1 expression initiates colonic tumorigenesis from cells outside the stem cell niche
Tumor angiogenesis: MMP-mediated induction of intravasation- and metastasis-sustaining neovasculature
Alternative preprocessing of RNA-Sequencing data in The Cancer Genome Atlas leads to improved analysis results
RegNetwork: an integrated database of transcriptional and post-transcriptional regulatory networks in human and mouse
Integrative Analyses of Colorectal Cancer Show Immunoscore Is a Stronger Predictor of Patient Survival Than Microsatellite Instability
CD34+ mesenchymal cells are a major component of the intestinal stem cells niche at homeostasis and after injury
Reference component analysis of single-cell transcriptomes elucidates cellular heterogeneity in human colorectal tumors
TRRUST v2: an expanded reference database of human and mouse transcriptional regulatory interactions
Single-Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in Head and Neck Cancer.
Durable Clinical Benefit With Nivolumab Plus Ipilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer
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