Spatially organized multicellular immune hubs in human colorectal cancer.

Karin PelkaNir Hacohen


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.


Oct 24, 2000·Immunological Reviews·J G CysterV N Ngo
Nov 2, 2002·Blood·Muneo NumasakiMichael T Lotze
Dec 18, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Robert N JorissenOliver M Sieber
Mar 19, 2009·Cancer Research·Helena HarlinThomas F Gajewski
Sep 11, 2009·The Journal of Clinical Investigation·Kellie A CharlesThorsten Hagemann
Apr 28, 2010·Gastroenterology·C Richard Boland, Ajay Goel
Jul 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·J-C DelvenneM Barahona
Jul 20, 2012·Nature·UNKNOWN Cancer Genome Atlas Network
Aug 17, 2012·Nature·Somasekar SeshagiriFrederic J de Sauvage
Apr 18, 2013·Source Code for Biology and Medicine·Yifeng Li, Alioune Ngom
Sep 24, 2013·Nature Methods·Simone PicelliRickard Sandberg
Mar 29, 2014·The Journal of Clinical Investigation·Alena GrosSteven A Rosenberg
Jun 14, 2014·Science·Anoop P PatelBradley E Bernstein
Jul 9, 2014·The Journal of Clinical Investigation·Yael HabermanLee A Denson
Apr 14, 2015·Nature Biotechnology·Rahul SatijaAviv Regev
Apr 29, 2015·Matrix Biology : Journal of the International Society for Matrix Biology·Elena I Deryugina, James P Quigley
Jun 2, 2015·The New England Journal of Medicine·Dung T LeLuis A Diaz
Sep 24, 2015·Scientific Reports·Pouya Esmailian, Mahdi Jalili
Oct 2, 2015·Database : the Journal of Biological Databases and Curation·Zhi-Ping LiuHulin Wu
Oct 13, 2015·Nature Medicine·Justin GuinneySabine Tejpar
Jan 16, 2016·Cell Systems·Arthur LiberzonPablo Tamayo
Mar 14, 2016·Trends in Molecular Medicine·Stephen K H Li, Alberto Martin
Jan 12, 2017·Proceedings of the National Academy of Sciences of the United States of America·Igor StzepourginskiLucie Peduto
Feb 25, 2017·The Journal of Experimental Medicine·Daniel ÖhlundDavid A Tuveson
Mar 3, 2017·PloS One·Jakob Nikolas KatherCleo-Aron Weis
Jun 27, 2017·The Journal of Clinical Investigation·Mark AyersTerrill K McClanahan
Aug 29, 2017·Nature Methods·Naomi HabibAviv Regev
Jan 23, 2018·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Michael J OvermanThierry André

❮ Previous
Next ❯


❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell eTOC

Cell is a scientific journal publishing research across a broad range of disciplines within the life sciences field. Discover the latest research from Cell here.

Related Papers

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Nicolas J LlosaFranck Housseau
The American Journal of Surgical Pathology
Cheryl L Wright, Ian D Stewart
Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc
Marion JaffrelotJanick Selves
© 2021 Meta ULC. All rights reserved