Recruitment and differentiation of conventional dendritic cell precursors in tumors.
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.
Diao
Jun
J
Toronto General Hospital Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Zhao
Jun
J
Winter
Erin
E
Cattral
Mark S
MS
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