title: Tumor-derived vaccines containing CD200 inhibit immune activation: implications for immunotherapy.
abstract: There are over 400 ongoing clinical trials using tumor-derived vaccines. This approach is especially attractive for many types of brain tumors, including glioblastoma, yet so far the clinical response is highly variable. One contributor to poor response is CD200, which acts as a checkpoint blockade, inducing immune tolerance. We demonstrate that, in response to vaccination, glioma-derived CD200 suppresses the anti-tumor immune response. In contrast, a CD200 peptide inhibitor that activates antigen-presenting cells overcomes immune tolerance. The addition of the CD200 inhibitor significantly increased leukocyte infiltration into the vaccine site, cytokine and chemokine production, and cytolytic activity. Our data therefore suggest that CD200 suppresses the immune system's response to vaccines, and that blocking CD200 could improve the efficacy of cancer immunotherapy.
authors.affiliation: University of Minnesota, Pediatrics, Division of Hematology and Oncology, Minneapolis, MN 55455, USA.
authors.forename: Zhengming
authors.initials: Z
authors.lastname: Xiong
authors.affiliation: University of Minnesota, Pediatrics, Division of Hematology and Oncology, Minneapolis, MN 55455, USA.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Ampudia-Mesias
authors.affiliation: University of Minnesota, Pediatrics, Division of Hematology and Oncology, Minneapolis, MN 55455, USA.
authors.forename: Rob
authors.initials: R
authors.lastname: Shaver
authors.affiliation: Departments of Neurosurgery & Pathology, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Craig M
authors.initials: CM
authors.lastname: Horbinski
authors.affiliation: University of Minnesota, Pediatrics, Division of Hematology and Oncology, Minneapolis, MN 55455, USA.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Moertel
authors.affiliation: University of Minnesota, Pediatrics, Division of Hematology and Oncology, Minneapolis, MN 55455, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Olin
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002465:Cell Movement; D002478:Cells, Cultured; D016543:Central Nervous System Neoplasms / Q000276:immunology / Q000628:therapy*; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D005909:Glioblastoma / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007108:Immune Tolerance; D007167:Immunotherapy / Q000379:methods*; D007962:Leukocytes / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D034741:RNA, Small Interfering / Q000235:genetics; D019139:Tumor Escape
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D016207:Cytokines; D034741:RNA, Small Interfering; C042739:antigens, CD200
keywords: CD200 protein; checkpoint blockade; immunotherapy