title: Natural killer cells eradicate galectin-1-deficient glioma in the absence of adaptive immunity.
abstract: Natural killer (NK) cells safeguard against early tumor formation by destroying transformed target cells in a process referred to as NK immune surveillance. However, the immune escape mechanisms used by malignant brain tumors to subvert this innate type of immune surveillance remain unclear. Here we show that malignant glioma cells suppress NK immune surveillance by overexpressing the β-galactoside-binding lectin galectin-1. Conversely, galectin-1-deficient glioma cells could be eradicated by host NK cells before the initiation of an antitumor T-cell response. In vitro experiments demonstrated that galectin-1-deficient GL26-Cit glioma cells are ∼3-fold more sensitive to NK-mediated tumor lysis than galectin-1-expressing cells. Our findings suggest that galectin-1 suppression in human glioma could improve patient survival by restoring NK immune surveillance that can eradicate glioma cells. Cancer Res; 74(18); 5079-90. ©2014 AACR.
authors.affiliation: Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, Michigan. Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Baker
authors.affiliation: Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, Michigan. Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan.
authors.forename: Peter
authors.initials: P
authors.lastname: Chockley
authors.affiliation: Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, Michigan. Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan.
authors.forename: Viveka Nand
authors.initials: VN
authors.lastname: Yadav
authors.affiliation: Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, Michigan. Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan.
authors.forename: Robert
authors.initials: R
authors.lastname: Doherty
authors.affiliation: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan.
authors.forename: Michael
authors.initials: M
authors.lastname: Ritt
authors.affiliation: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan. Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan.
authors.forename: Sivaraj
authors.initials: S
authors.lastname: Sivaramakrishnan
authors.affiliation: Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, Michigan. Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Castro
authors.affiliation: Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, Michigan. Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan. pedrol@umich.edu.
authors.forename: Pedro R
authors.initials: PR
authors.lastname: Lowenstein
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000818:Animals; D001932:Brain Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D005260:Female; D037483:Galectin 1 / Q000172:deficiency* / Q000276:immunology / Q000378:metabolism; D005910:Glioma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D006801:Humans; D007157:Immunologic Surveillance; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D037483:Galectin 1