title: Dendritic Cell-Based Vaccines that Utilize Myeloid Rather than Plasmacytoid Cells Offer a Superior Survival Advantage in Malignant Glioma.
abstract: Dendritic cells (DCs) are professional APCs that are traditionally divided into two distinct subsets, myeloid DC (mDCs) and plasmacytoid DC (pDCs). pDCs are known for their ability to secrete large amounts of IFN-α. Apart from IFN-α production, pDCs can also process Ag and induce T cell immunity or tolerance. In several solid tumors, pDCs have been shown to play a critical role in promoting tumor immunosuppression. We investigated the role of pDCs in the process of glioma progression in the syngeneic murine model of glioma. We show that glioma-infiltrating pDCs are the major APC in glioma and are deficient in IFN-α secretion (p < 0.05). pDC depletion leads to increased survival of the mice bearing intracranial tumor by decreasing the number of regulatory T cells (Tregs) and by decreasing the suppressive capabilities of Tregs. We subsequently compared the ability of mDCs and pDCs to generate effective antiglioma immunity in a GL261-OVA mouse model of glioma. Our data suggest that mature pDCs and mDCs isolated from naive mice can be effectively activated and loaded with SIINFEKL Ag in vitro. Upon intradermal injection in the hindleg, a fraction of both types of DCs migrate to the brain and lymph nodes. Compared to mice vaccinated with pDC or control mice, mice vaccinated with mDCs generate a robust Th1 type immune response, characterized by high frequency of CD4(+)T-bet(+) T cells and CD8(+)SIINFEKEL(+) T cells. This robust antitumor T cell response results in tumor eradication and long-term survival in 60% of the animals (p < 0.001).
authors.affiliation: Brain Tumor Center, University of Chicago Pritzker School of Medicine, Chicago, IL 60637; and.
authors.forename: Mahua
authors.initials: M
authors.lastname: Dey
authors.affiliation: Brain Tumor Center, University of Chicago Pritzker School of Medicine, Chicago, IL 60637; and.
authors.forename: Alan L
authors.initials: AL
authors.lastname: Chang
authors.affiliation: Brain Tumor Center, University of Chicago Pritzker School of Medicine, Chicago, IL 60637; and.
authors.forename: Jason
authors.initials: J
authors.lastname: Miska
authors.affiliation: Brain Tumor Center, University of Chicago Pritzker School of Medicine, Chicago, IL 60637; and.
authors.forename: Derek A
authors.initials: DA
authors.lastname: Wainwright
authors.affiliation: Brain Tumor Center, University of Chicago Pritzker School of Medicine, Chicago, IL 60637; and.
authors.forename: Atique U
authors.initials: AU
authors.lastname: Ahmed
authors.affiliation: Brain Tumor Center, University of Chicago Pritzker School of Medicine, Chicago, IL 60637; and.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Balyasnikova
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL 60637.
authors.forename: Peter
authors.initials: P
authors.lastname: Pytel
authors.affiliation: Brain Tumor Center, University of Chicago Pritzker School of Medicine, Chicago, IL 60637; and.
authors.forename: Yu
authors.initials: Y
authors.lastname: Han
authors.affiliation: Brain Tumor Center, University of Chicago Pritzker School of Medicine, Chicago, IL 60637; and.
authors.forename: Alex
authors.initials: A
authors.lastname: Tobias
authors.affiliation: Brain Tumor Center, University of Chicago Pritzker School of Medicine, Chicago, IL 60637; and.
authors.forename: Lingjiao
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Brain Tumor Center, University of Chicago Pritzker School of Medicine, Chicago, IL 60637; and.
authors.forename: Jian
authors.initials: J
authors.lastname: Qiao
authors.affiliation: Brain Tumor Center, University of Chicago Pritzker School of Medicine, Chicago, IL 60637; and mlesniak@surgery.bsd.uchicago.edu.
authors.forename: Maciej S
authors.initials: MS
authors.lastname: Lesniak
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001921:Brain / Q000276:immunology / Q000473:pathology; D001932:Brain Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D002452:Cell Count; D019070:Cell Lineage / Q000276:immunology*; D002465:Cell Movement; D003713:Dendritic Cells / Q000145:classification / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D005910:Glioma / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000276:immunology; D016898:Interferon-alpha / Q000096:biosynthesis; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000276:immunology / Q000473:pathology; D010047:Ovalbumin / Q000737:chemistry / Q000276:immunology; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D016019:Survival Analysis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000473:pathology; D014611:Vaccination
chemical_list: D019496:Cancer Vaccines; D016056:Immunodominant Epitopes; D016898:Interferon-alpha; C110366:OVA-8; D010446:Peptide Fragments; D010047:Ovalbumin