title: Recruitment and differentiation of conventional dendritic cell precursors in tumors.
abstract: The origin of dendritic cells (DCs) in tumors remains obscure. Recent studies indicate that conventional DCs (cDCs) in lymphoid tissues arise from a distinct population of committed cDC precursors (pre-cDCs) that originate in bone marrow and migrate via blood. In this study, we show that pre-cDCs are precursors for cDCs in tumors. Pre-cDCs from tumors, bone marrow, and spleen exhibit similar morphologic, immunophenotypic, and functional properties. Adoptive transfer studies show that bone marrow pre-cDCs migrate from blood into the tumor where they generate cDCs. The chemokine CCL3, which is markedly upregulated in tumors, promotes pre-cDC recruitment. Both pre-cDCs and their cDC progeny actively proliferate within the tumor. cDCs that arise from pre-cDCs in tumors express lower levels of CD11c and MHC class II as compared with those in spleen; however, there was no difference in their abilities to respond to maturation stimuli or activate Ag-specific lymphocytes in vitro. Our study provides the first evidence supporting a role for pre-cDCs in DC development in tumors and suggests a potential target for cancer immunotherapy.
authors.affiliation: Toronto General Hospital Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jun
authors.initials: J
authors.lastname: Diao
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.forename: Erin
authors.initials: E
authors.lastname: Winter
authors.forename: Mark S
authors.initials: MS
authors.lastname: Cattral
mesh_terms: D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation / Q000276:immunology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000276:immunology*; D018920:Coculture Techniques; D003110:Colonic Neoplasms / Q000276:immunology / Q000473:pathology; D003713:Dendritic Cells / Q000145:classification / Q000276:immunology* / Q000473:pathology; D008297:Male; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000276:immunology* / Q000473:pathology