Spatially organized multicellular immune hubs in human colorectal cancer,Cell

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Spatially organized multicellular immune hubs in human colorectal cancer
Cell ( IF 45.5 ) Pub Date : 2021-08-26 , DOI: 10.1016/j.cell.2021.08.003
Karin Pelka ₁ , Matan Hofree ₂ , Jonathan H Chen ₃ , Siranush Sarkizova ₄ , Joshua D Pirl ₄ , Vjola Jorgji ₅ , Alborz Bejnood ₂ , Danielle Dionne ₂ , William H Ge ₄ , Katherine H Xu ₆ , Sherry X Chao ₇ , Daniel R Zollinger ₈ , David J Lieb ₄ , Jason W Reeves ₈ , Christopher A Fuhrman ₈ , Margaret L Hoang ₈ , Toni Delorey ₂ , Lan T Nguyen ₂ , Julia Waldman ₂ , Max Klapholz ₉ , Isaac Wakiro ₁₀ , Ofir Cohen ₁₁ , Julian Albers ₄ , Christopher S Smillie ₂ , Michael S Cuoco ₂ , Jingyi Wu ₁₀ , Mei-Ju Su ₁₀ , Jason Yeung ₁₀ , Brinda Vijaykumar ₁₂ , Angela M Magnuson ₁₂ , Natasha Asinovski ₁₂ , Tabea Moll ₁₃ , Max N Goder-Reiser ₁₃ , Anise S Applebaum ₁₃ , Lauren K Brais ₁₄ , Laura K DelloStritto ₁₀ , Sarah L Denning ₁₄ , Susannah T Phillips ₁₃ , Emma K Hill ₁₄ , Julia K Meehan ₁₄ , Dennie T Frederick ₁₃ , Tatyana Sharova ₁₃ , Abhay Kanodia ₁₀ , Ellen Z Todres ₄ , Judit Jané-Valbuena ₂ , Moshe Biton ₁₅ , Benjamin Izar ₁₆ , Conner D Lambden ₉ , Thomas E Clancy ₁₇ , Ronald Bleday ₁₇ , Nelya Melnitchouk ₁₇ , Jennifer Irani ₁₇ , Hiroko Kunitake ₁₈ , David L Berger ₁₈ , Amitabh Srivastava ₁₉ , Jason L Hornick ₁₉ , Shuji Ogino ₂₀ , Asaf Rotem ₁₀ , Sébastien Vigneau ₁₀ , Bruce E Johnson ₂₁ , Ryan B Corcoran ₂₂ , Arlene H Sharpe ₂₃ , Vijay K Kuchroo ₉ , Kimmie Ng ₂₄ , Marios Giannakis ₂₅ , Linda T Nieman ₆ , Genevieve M Boland ₂₆ , Andrew J Aguirre ₂₅ , Ana C Anderson ₉ , Orit Rozenblatt-Rosen ₂ , Aviv Regev ₂₇ , Nir Hacohen ₂₈

Affiliation

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.
Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
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.
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.
Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA.
Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA; Department of Biomedical Informatics, HMS, Boston, MA, USA.
NanoString Technologies Inc., Seattle, WA, USA.
Evergrande Center for Immunologic Diseases, HMS and Brigham and Women's Hospital (BWH), Boston, MA, USA.
Center for Cancer Genomics, Department of Medical Oncology, Dana-Farber Cancer Institute (DFCI), Boston, MA, USA.
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.
Department of Immunology, HMS, Boston, MA, USA.
Clinical Research Center, MGH, Boston, MA, USA.
Clinical Research Center, DFCI, Boston, MA, USA.
Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Molecular Biology, MGH, Boston, MA, USA.
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.
Department of Surgery, BWH, Boston, MA, USA.
Department of Surgery, MGH, Boston, MA, USA.
Department of Pathology, BWH, Boston, MA, USA.
Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA; Department of Pathology, BWH, Boston, 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.
Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA; Department of Medicine, HMS, Boston, MA, USA.
Evergrande Center for Immunologic Diseases, HMS and Brigham and Women's Hospital (BWH), Boston, MA, USA; Department of Immunology, Blavatnik Institute, HMS, Boston, MA, USA.
Department of Medical Oncology, DFCI, Boston, MA, USA.
Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA; Department of Medical Oncology, DFCI, Boston, MA, USA.
Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA; Department of Surgery, MGH, Boston, MA, USA.
Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Howard Hughes Medical Institute and Koch Institute for Integrative Cancer Research, Department of Biology, MIT, Cambridge, MA, USA.
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 Immunology, HMS, Boston, MA, USA.

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.

更新日期：2021-09-02

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