title: Zinc in innate and adaptive tumor immunity.
abstract: Zinc is important. It is the second most abundant trace metal with 2-4 grams in humans. It is an essential trace element, critical for cell growth, development and differentiation, DNA synthesis, RNA transcription, cell division, and cell activation. Zinc deficiency has adverse consequences during embryogenesis and early childhood development, particularly on immune functioning. It is essential in members of all enzyme classes, including over 300 signaling molecules and transcription factors. Free zinc in immune and tumor cells is regulated by 14 distinct zinc importers (ZIP) and transporters (ZNT1-8). Zinc depletion induces cell death via apoptosis (or necrosis if apoptotic pathways are blocked) while sufficient zinc levels allows maintenance of autophagy. Cancer cells have upregulated zinc importers, and frequently increased zinc levels, which allow them to survive. Based on this novel synthesis, approaches which locally regulate zinc levels to promote survival of immune cells and/or induce tumor apoptosis are in order.
authors.affiliation: Department of Surgery, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
authors.forename: Erica
authors.initials: E
authors.lastname: John
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Laskow
authors.forename: William J
authors.initials: WJ
authors.lastname: Buchser
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Pitt
authors.forename: Per H
authors.initials: PH
authors.lastname: Basse
authors.forename: Lisa H
authors.initials: LH
authors.lastname: Butterfield
authors.forename: Pawel
authors.initials: P
authors.lastname: Kalinski
authors.forename: Michael T
authors.initials: MT
authors.lastname: Lotze
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D017209:Apoptosis; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology*; D015398:Signal Transduction; D015032:Zinc / Q000172:deficiency / Q000276:immunology* / Q000378:metabolism
chemical_list: D015032:Zinc