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Cell ; 184(18): 4734-4752.e20, 2021 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-34450029

RESUMEN

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.


Asunto(s)
Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/patología , Proteínas Morfogenéticas Óseas/metabolismo , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/patología , Compartimento Celular , Línea Celular Tumoral , Quimiocinas/metabolismo , Estudios de Cohortes , Neoplasias Colorrectales/genética , Reparación de la Incompatibilidad de ADN/genética , Células Endoteliales/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunidad , Inflamación/patología , Monocitos/patología , Células Mieloides/patología , Neutrófilos/patología , Células del Estroma/metabolismo , Linfocitos T/metabolismo , Transcripción Genética
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