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Stromal remodeling regulates dendritic cell abundance and activity in the tumor microenvironment.
Papadas, Athanasios; Deb, Gauri; Cicala, Alexander; Officer, Adam; Hope, Chelsea; Pagenkopf, Adam; Flietner, Evan; Morrow, Zachary T; Emmerich, Philip; Wiesner, Joshua; Arauz, Garrett; Bansal, Varun; Esbona, Karla; Capitini, Christian M; Matkowskyj, Kristina A; Deming, Dustin A; Politi, Katerina; Abrams, Scott I; Harismendy, Olivier; Asimakopoulos, Fotis.
Affiliation
  • Papadas A; Division of Blood and Marrow Transplantation, Department of Medicine, University of California, San Diego (UCSD), La Jolla, CA, USA; Moores Cancer Center, University of California, San Diego (UCSD), La Jolla, CA, USA; Cellular and Molecular Pathology Graduate Program, University of Wisconsin-Madison
  • Deb G; Division of Blood and Marrow Transplantation, Department of Medicine, University of California, San Diego (UCSD), La Jolla, CA, USA; Moores Cancer Center, University of California, San Diego (UCSD), La Jolla, CA, USA.
  • Cicala A; Division of Blood and Marrow Transplantation, Department of Medicine, University of California, San Diego (UCSD), La Jolla, CA, USA; Moores Cancer Center, University of California, San Diego (UCSD), La Jolla, CA, USA.
  • Officer A; Moores Cancer Center, University of California, San Diego (UCSD), La Jolla, CA, USA; Division of Biomedical Informatics, Department of Medicine, University of California, San Diego (UCSD), Moores Cancer Center, La Jolla, CA, USA; Bioinformatics and Systems Biology Graduate Program, University of Cal
  • Hope C; Cellular and Molecular Pathology Graduate Program, University of Wisconsin-Madison, Madison, WI, USA; Division of Hematology and Oncology, Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA; UW Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA.
  • Pagenkopf A; Division of Hematology and Oncology, Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA; UW Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA.
  • Flietner E; Cellular and Molecular Pathology Graduate Program, University of Wisconsin-Madison, Madison, WI, USA; Division of Hematology and Oncology, Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA; UW Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA.
  • Morrow ZT; Division of Hematology and Oncology, Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA; UW Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA.
  • Emmerich P; Cellular and Molecular Pathology Graduate Program, University of Wisconsin-Madison, Madison, WI, USA; UW Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA.
  • Wiesner J; Division of Blood and Marrow Transplantation, Department of Medicine, University of California, San Diego (UCSD), La Jolla, CA, USA; Moores Cancer Center, University of California, San Diego (UCSD), La Jolla, CA, USA.
  • Arauz G; Division of Blood and Marrow Transplantation, Department of Medicine, University of California, San Diego (UCSD), La Jolla, CA, USA; Moores Cancer Center, University of California, San Diego (UCSD), La Jolla, CA, USA.
  • Bansal V; Division of Blood and Marrow Transplantation, Department of Medicine, University of California, San Diego (UCSD), La Jolla, CA, USA; Moores Cancer Center, University of California, San Diego (UCSD), La Jolla, CA, USA.
  • Esbona K; UW Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA; Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI, USA.
  • Capitini CM; UW Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA; Division of Hematology and Oncology, Department of Pediatrics, University of Wisconsin-Madison, Madison, WI, USA.
  • Matkowskyj KA; UW Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA; Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI, USA.
  • Deming DA; Division of Hematology and Oncology, Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA; UW Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA; McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WI, USA.
  • Politi K; Department of Pathology, Yale School of Medicine, New Haven, CT, USA; Department of Medicine, Yale School of Medicine, New Haven, CT, USA; Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA.
  • Abrams SI; Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
  • Harismendy O; Moores Cancer Center, University of California, San Diego (UCSD), La Jolla, CA, USA; Division of Biomedical Informatics, Department of Medicine, University of California, San Diego (UCSD), Moores Cancer Center, La Jolla, CA, USA.
  • Asimakopoulos F; Division of Blood and Marrow Transplantation, Department of Medicine, University of California, San Diego (UCSD), La Jolla, CA, USA; Moores Cancer Center, University of California, San Diego (UCSD), La Jolla, CA, USA. Electronic address: fotis@health.ucsd.edu.
Cell Rep ; 40(7): 111201, 2022 08 16.
Article in En | MEDLINE | ID: mdl-35977482
ABSTRACT
Stimulatory type 1 conventional dendritic cells (cDC1s) engage in productive interactions with CD8+ effectors along tumor-stroma boundaries. The paradoxical accumulation of "poised" cDC1s within stromal sheets is unlikely to simply reflect passive exclusion from tumor cores. Drawing parallels with embryonic morphogenesis, we hypothesized that invasive margin stromal remodeling generates developmentally conserved cell fate cues that regulate cDC1 behavior. We find that, in human T cell-inflamed tumors, CD8+ T cells penetrate tumor nests, whereas cDC1s are confined within adjacent stroma that recurrently displays site-specific proteolysis of the matrix proteoglycan versican (VCAN), an essential organ-sculpting modification in development. VCAN is necessary, and its proteolytic fragment (matrikine) versikine is sufficient for cDC1 accumulation. Versikine does not influence tumor-seeding pre-DC differentiation; rather, it orchestrates a distinctive cDC1 activation program conferring exquisite sensitivity to DNA sensing, supported by atypical innate lymphoid cells. Thus, peritumoral stroma mimicking embryonic provisional matrix remodeling regulates cDC1 abundance and activity to elicit T cell-inflamed tumor microenvironments.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Tumor Microenvironment / Neoplasms Limits: Humans Language: En Journal: Cell Rep Year: 2022 Type: Article
Fulltext
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Tumor Microenvironment / Neoplasms Limits: Humans Language: En Journal: Cell Rep Year: 2022 Type: Article