PMID- 26026061 OWN - NLM STAT- MEDLINE DCOM- 20150831 LR - 20220429 IS - 1550-6606 (Electronic) IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 195 IP - 1 DP - 2015 Jul 1 TI - Dendritic Cell-Based Vaccines that Utilize Myeloid Rather than Plasmacytoid Cells Offer a Superior Survival Advantage in Malignant Glioma. PG - 367-76 LID - 10.4049/jimmunol.1401607 [doi] AB - 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-alpha. Apart from IFN-alpha 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-alpha 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). CI - Copyright (c) 2015 by The American Association of Immunologists, Inc. FAU - Dey, Mahua AU - Dey M AD - Brain Tumor Center, University of Chicago Pritzker School of Medicine, Chicago, IL 60637; and. FAU - Chang, Alan L AU - Chang AL AD - Brain Tumor Center, University of Chicago Pritzker School of Medicine, Chicago, IL 60637; and. FAU - Miska, Jason AU - Miska J AD - Brain Tumor Center, University of Chicago Pritzker School of Medicine, Chicago, IL 60637; and. FAU - Wainwright, Derek A AU - Wainwright DA AD - Brain Tumor Center, University of Chicago Pritzker School of Medicine, Chicago, IL 60637; and. FAU - Ahmed, Atique U AU - Ahmed AU AD - Brain Tumor Center, University of Chicago Pritzker School of Medicine, Chicago, IL 60637; and. FAU - Balyasnikova, Irina V AU - Balyasnikova IV AD - Brain Tumor Center, University of Chicago Pritzker School of Medicine, Chicago, IL 60637; and. FAU - Pytel, Peter AU - Pytel P AD - Department of Pathology, University of Chicago, Chicago, IL 60637. FAU - Han, Yu AU - Han Y AD - Brain Tumor Center, University of Chicago Pritzker School of Medicine, Chicago, IL 60637; and. FAU - Tobias, Alex AU - Tobias A AD - Brain Tumor Center, University of Chicago Pritzker School of Medicine, Chicago, IL 60637; and. FAU - Zhang, Lingjiao AU - Zhang L AD - Brain Tumor Center, University of Chicago Pritzker School of Medicine, Chicago, IL 60637; and. FAU - Qiao, Jian AU - Qiao J AD - Brain Tumor Center, University of Chicago Pritzker School of Medicine, Chicago, IL 60637; and. FAU - Lesniak, Maciej S AU - Lesniak MS AD - Brain Tumor Center, University of Chicago Pritzker School of Medicine, Chicago, IL 60637; and mlesniak@surgery.bsd.uchicago.edu. LA - eng GR - R01CA122930/CA/NCI NIH HHS/United States GR - R00 NS082381/NS/NINDS NIH HHS/United States GR - U01NS077388/NS/NINDS NIH HHS/United States GR - RR01CA138587/CA/NCI NIH HHS/United States GR - T32 CA009594/CA/NCI NIH HHS/United States GR - R01 NS077388/NS/NINDS NIH HHS/United States GR - UL1 TR001422/TR/NCATS NIH HHS/United States GR - R25NS065744/NS/NINDS NIH HHS/United States GR - R01 CA138587/CA/NCI NIH HHS/United States GR - R25 NS065744/NS/NINDS NIH HHS/United States GR - F32 NS073366/NS/NINDS NIH HHS/United States GR - P30 CA060553/CA/NCI NIH HHS/United States GR - K99 NS082381/NS/NINDS NIH HHS/United States GR - R01 CA122930/CA/NCI NIH HHS/United States GR - R01NS077388/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20150529 PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Cancer Vaccines) RN - 0 (Immunodominant Epitopes) RN - 0 (Interferon-alpha) RN - 0 (OVA-8) RN - 0 (Peptide Fragments) RN - 9006-59-1 (Ovalbumin) SB - IM MH - Adaptive Immunity MH - Animals MH - Brain/immunology/pathology MH - Brain Neoplasms/immunology/mortality/pathology/*therapy MH - Cancer Vaccines/*administration & dosage/immunology MH - Cell Count MH - Cell Lineage/*immunology MH - Cell Movement MH - Dendritic Cells/classification/*immunology/pathology/transplantation MH - Glioma/immunology/mortality/pathology/*therapy MH - Immunodominant Epitopes/chemistry/immunology MH - Interferon-alpha/biosynthesis MH - Lymph Nodes/immunology/pathology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Myeloid Cells/immunology/pathology MH - Ovalbumin/chemistry/immunology MH - Peptide Fragments/chemistry/immunology MH - Survival Analysis MH - T-Lymphocytes, Regulatory/immunology/pathology MH - Th1 Cells/immunology/pathology MH - Vaccination PMC - PMC4475664 MID - NIHMS688914 COIS- Disclosures The authors have no financial conflicts of interest. EDAT- 2015/05/31 06:00 MHDA- 2015/09/01 06:00 PMCR- 2016/07/01 CRDT- 2015/05/31 06:00 PHST- 2014/06/24 00:00 [received] PHST- 2015/05/02 00:00 [accepted] PHST- 2015/05/31 06:00 [entrez] PHST- 2015/05/31 06:00 [pubmed] PHST- 2015/09/01 06:00 [medline] PHST- 2016/07/01 00:00 [pmc-release] AID - jimmunol.1401607 [pii] AID - 10.4049/jimmunol.1401607 [doi] PST - ppublish SO - J Immunol. 2015 Jul 1;195(1):367-76. doi: 10.4049/jimmunol.1401607. Epub 2015 May 29.