title: Examination of MARCO activity on dendritic cell phenotype and function using a gene knockout mouse.
abstract: We have reported the upregulation of MARCO, a member of the class A scavenger receptor family, on the surface of murine and human dendritic cells (DCs) pulsed with tumor lysates. Exposure of murine tumor lysate-pulsed DCs to an anti-MARCO antibody led to loss of dendritic-like processes and enhanced migratory capacity. In this study, we have further examined the biological and therapeutic implications of MARCO expression by DCs. DCs generated from the bone marrow (bm) of MARCO knockout (MARCO⁻/⁻) mice were phenotypically similar to DCs generated from the bm of wild-type mice and produced normal levels of IL-12 and TNF-α when exposed to LPS. MARCO⁻/⁻ DCs demonstrated enhanced migratory capacity in response to CCL-21 in vitro. After subcutaneous injection into mice, MARCO⁻/⁻ TP-DCs migrated more efficiently to the draining lymph node leading to enhanced generation of tumor-specific IFN-γ producing T cells and improved tumor regression and survival in B16 melanoma-bearing mice. These results support targeting MARCO on the surface of DCs to improve trafficking and induction of anti-tumor immunity.
authors.affiliation: Immunology Program, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, United States of America.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Komine
authors.forename: Lisa
authors.initials: L
authors.lastname: Kuhn
authors.forename: Norimasa
authors.initials: N
authors.lastname: Matsushita
authors.forename: James J
authors.initials: JJ
authors.lastname: Mulé
authors.forename: Shari
authors.initials: S
authors.lastname: Pilon-Thomas
mesh_terms: D000818:Animals; D002465:Cell Movement; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000276:immunology; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011971:Receptors, Immunologic / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D016207:Cytokines; C092228:Marco protein, mouse; D011971:Receptors, Immunologic; D007371:Interferon-gamma