title: Aminobisphosphonates inhibit dendritic cell-mediated antigen-specific activation of CD1d-restricted iNKT cells.
abstract: CD1d-restricted invariant natural killer T (iNKT) cells constitute an important immunoregulatory T cell subset that can be activated by the synthetic glycolipid α-galactosylceramide (α-GalCer) and initiate antitumor immune responses. As cancer patients are frequently treated with aminobisphosphonates (NBP), it is relevant to determine possible effects of NBP on CD1d-restricted glycolipid Ag-presentation to iNKT cells. We report a striking reduction of α-GalCer-induced iNKT cell activation by monocyte derived dendritic cells (moDC) upon their exposure to NBP during maturation. We found that production of apolipoprotein E (apoE), which is a known facilitator of trans-membrane transport of exogenously derived glycolipids, was significantly diminished in moDC exposed to NBP. As the inhibitory effect of NBP on iNKT cell activation was alleviated by exogenous apoE, our data indicate that reduced apoE production by antigen presenting cells (APC) through NBP limits glycolipid-induced iNKT cell activation. This should be taken into account in the design of iNKT cell-based anti-cancer therapies.
authors: Department of Medical Oncology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. Electronic address: f.schneiders@vumc.nl.
authors: Famke L
authors: FL
authors: Schneiders
authors: Department of Medical Oncology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
authors: Charlotte M
authors: CM
authors: Huijts
authors: Department of Medical Oncology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
authors: Aslihan
authors: A
authors: Mantici
authors: Department of Medical Oncology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
authors: Mica A C
authors: MA
authors: Menks
authors: Institut National de la Santé et de la Recherche Médicale, UMR892, Centre de Recherche en Cancérologie Nantes-Angers, Nantes, France.
authors: Emmanuel
authors: E
authors: Scotet
authors: Department of Clinical Chemistry, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; Department of Psychiatry, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
authors: Rob
authors: R
authors: Veerhuis
authors: Department of Medical Oncology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
authors: Henk M W
authors: HM
authors: Verheul
authors: Department of Medical Oncology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
authors: Tanja D
authors: TD
authors: de Gruijl
authors: Department of Medical Oncology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. Electronic address: jj.vandervliet@vumc.nl.
authors: Hans J
authors: HJ
authors: van der Vliet
mesh_terms: D000588:Amines / Q000494:pharmacology*; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology; D055610:Antigens, CD1d / Q000276:immunology; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D002460:Cell Line; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D004164:Diphosphonates / Q000494:pharmacology*; D005699:Galactosylceramides / Q000494:pharmacology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D055611:Natural Killer T-Cells / Q000187:drug effects* / Q000276:immunology
chemical_list: D000588:Amines; D055610:Antigens, CD1d; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D005699:Galactosylceramides; C493154:alpha-galactosylceramide
keywords: Aminobisphosphonates; Apolipoprotein E (apoE); dendritic cell (DC); iNKT; α-GalCer