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Spatially organized multicellular immune hubs in human colorectal cancer.
Pelka, Karin; Hofree, Matan; Chen, Jonathan H; Sarkizova, Siranush; Pirl, Joshua D; Jorgji, Vjola; Bejnood, Alborz; Dionne, Danielle; Ge, William H; Xu, Katherine H; Chao, Sherry X; Zollinger, Daniel R; Lieb, David J; Reeves, Jason W; Fuhrman, Christopher A; Hoang, Margaret L; Delorey, Toni; Nguyen, Lan T; Waldman, Julia; Klapholz, Max; Wakiro, Isaac; Cohen, Ofir; Albers, Julian; Smillie, Christopher S; Cuoco, Michael S; Wu, Jingyi; Su, Mei-Ju; Yeung, Jason; Vijaykumar, Brinda; Magnuson, Angela M; Asinovski, Natasha; Moll, Tabea; Goder-Reiser, Max N; Applebaum, Anise S; Brais, Lauren K; DelloStritto, Laura K; Denning, Sarah L; Phillips, Susannah T; Hill, Emma K; Meehan, Julia K; Frederick, Dennie T; Sharova, Tatyana; Kanodia, Abhay; Todres, Ellen Z; Jané-Valbuena, Judit; Biton, Moshe; Izar, Benjamin; Lambden, Conner D; Clancy, Thomas E; Bleday, Ronald.
Affiliation
  • Pelka K; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA; Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA.
  • Hofree M; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Chen JH; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA; Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA; Department of Pathology, MGH, Boston, MA, USA.
  • Sarkizova S; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
  • Pirl JD; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
  • Jorgji V; Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA; Department of Pathology, MGH, Boston, MA, USA.
  • Bejnood A; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Dionne D; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Ge WH; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
  • Xu KH; Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA.
  • Chao SX; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA; Department of Biomedical Informatics, HMS, Boston, MA, USA.
  • Zollinger DR; NanoString Technologies Inc., Seattle, WA, USA.
  • Lieb DJ; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
  • Reeves JW; NanoString Technologies Inc., Seattle, WA, USA.
  • Fuhrman CA; NanoString Technologies Inc., Seattle, WA, USA.
  • Hoang ML; NanoString Technologies Inc., Seattle, WA, USA.
  • Delorey T; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Nguyen LT; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Waldman J; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Klapholz M; Evergrande Center for Immunologic Diseases, HMS and Brigham and Women's Hospital (BWH), Boston, MA, USA.
  • Wakiro I; Center for Cancer Genomics, Department of Medical Oncology, Dana-Farber Cancer Institute (DFCI), Boston, MA, USA.
  • Cohen O; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA; Center for Cancer Genomics, Department of Medical Oncology, Dana-Farber Cancer Institute (DFCI), Boston, MA, USA; Department of Medical Oncology, DFCI, Boston, MA, USA.
  • Albers J; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
  • Smillie CS; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Cuoco MS; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Wu J; Center for Cancer Genomics, Department of Medical Oncology, Dana-Farber Cancer Institute (DFCI), Boston, MA, USA.
  • Su MJ; Center for Cancer Genomics, Department of Medical Oncology, Dana-Farber Cancer Institute (DFCI), Boston, MA, USA.
  • Yeung J; Center for Cancer Genomics, Department of Medical Oncology, Dana-Farber Cancer Institute (DFCI), Boston, MA, USA.
  • Vijaykumar B; Department of Immunology, HMS, Boston, MA, USA.
  • Magnuson AM; Department of Immunology, HMS, Boston, MA, USA.
  • Asinovski N; Department of Immunology, HMS, Boston, MA, USA.
  • Moll T; Clinical Research Center, MGH, Boston, MA, USA.
  • Goder-Reiser MN; Clinical Research Center, MGH, Boston, MA, USA.
  • Applebaum AS; Clinical Research Center, MGH, Boston, MA, USA.
  • Brais LK; Clinical Research Center, DFCI, Boston, MA, USA.
  • DelloStritto LK; Center for Cancer Genomics, Department of Medical Oncology, Dana-Farber Cancer Institute (DFCI), Boston, MA, USA.
  • Denning SL; Clinical Research Center, DFCI, Boston, MA, USA.
  • Phillips ST; Clinical Research Center, MGH, Boston, MA, USA.
  • Hill EK; Clinical Research Center, DFCI, Boston, MA, USA.
  • Meehan JK; Clinical Research Center, DFCI, Boston, MA, USA.
  • Frederick DT; Clinical Research Center, MGH, Boston, MA, USA.
  • Sharova T; Clinical Research Center, MGH, Boston, MA, USA.
  • Kanodia A; Center for Cancer Genomics, Department of Medical Oncology, Dana-Farber Cancer Institute (DFCI), Boston, MA, USA.
  • Todres EZ; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
  • Jané-Valbuena J; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Biton M; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Molecular Biology, MGH, Boston, MA, USA.
  • Izar B; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Center for Cancer Genomics, Department of Medical Oncology, Dana-Farber Cancer Institute (DFCI), Boston, MA, USA; Department of Medical Oncology, DFCI, Boston, MA, USA.
  • Lambden CD; Evergrande Center for Immunologic Diseases, HMS and Brigham and Women's Hospital (BWH), Boston, MA, USA.
  • Clancy TE; Department of Surgery, BWH, Boston, MA, USA.
  • Bleday R; Department of Surgery, BWH, Boston, MA, USA.
Cell ; 184(18): 4734-4752.e20, 2021 09 02.
Article in En | MEDLINE | ID: mdl-34450029
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Colorectal Neoplasms Type of study: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Humans Language: En Journal: Cell Year: 2021 Type: Article Affiliation country: United States
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Colorectal Neoplasms Type of study: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Humans Language: En Journal: Cell Year: 2021 Type: Article Affiliation country: United States