Home LiteratureArticle Details

PMID: 20150362 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

TGF-beta downregulates the activating receptor NKG2D on NK cells and CD8+ T cells in glioma patients.

Neuro-oncology ·Vol. 12 ·No. 1 ·2010-01-00 ·Pages 7-13

Crane CA, Han SJ, Barry JJ, Ahn BJ, Lanier LL, Parsa AT

Abstract

The activating receptor NKG2D, expressed by natural killer (NK) cells and CD8(+) T cells, has a role in the specific killing of transformed cells. We examined NKG2D expression in patients with glioblastoma multiforme and found that NKG2D was downregulated on NK cells and CD8(+) T cells. Expression of NKG2D on lymphocytes significantly increased following tumor resection and correlated with an increased ability to kill NKG2D ligand-positive tumor targets. Despite the presence of soluble NKG2D ligands in the sera of glioblastoma patients, NKG2D downregulation was primarily caused by tumor-derived tumor growth factor-beta, suggesting that blocking of this cytokine may have therapeutic benefit.

MeSH Terms

Brain Neoplasms/immunology,metabolism CD8-Positive T-Lymphocytes/immunology,metabolism Cell Separation Cytotoxicity, Immunologic/immunology Down-Regulation Enzyme-Linked Immunosorbent Assay Flow Cytometry Fluorescent Antibody Technique Gene Expression Regulation, Neoplastic/genetics Glioma/immunology,metabolism Humans Immune Tolerance/physiology Killer Cells, Natural/immunology,metabolism NK Cell Lectin-Like Receptor Subfamily K/biosynthesis Reverse Transcriptase Polymerase Chain Reaction Transforming Growth Factor beta/metabolism

Chemicals

KLRK1 protein, human NK Cell Lectin-Like Receptor Subfamily K Transforming Growth Factor beta

Authors & Affiliations

6 authors, click to expand affiliations / ORCID

Crane Courtney A

Department of Neurological Surgery, University of California-San Francisco, San Francisco, California 94143, USA.

Han Seunggu J

Barry Jeffery J

Ahn Brian J

Lanier Lewis L

Parsa Andrew T

References (20)

20 references, click to expand

Normal adult ramified microglia separated from other central nervous system macrophages by flow cytometric sorting. Phenotypic differences defined and direct ex vivo antigen presentation to myelin basic protein-reactive CD4+ T cells compared.
J Immunol. 1995 May 1;154(9):4309-21 PMID: 7722289
Malignancy after kidney transplantation: results of 400 patients from a single center.
Clin Transplant. 2008 Jul-Aug;22(4):424-7 PMID: 18312442
Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation.
Nature. 2002 Oct 17;419(6908):734-8 PMID: 12384702
Enhanced in vivo growth and resistance to rejection of tumor cells expressing dominant negative IFN gamma receptors.
Immunity. 1994 Sep;1(6):447-56 PMID: 7895156
ULBPs, novel MHC class I-related molecules, bind to CMV glycoprotein UL16 and stimulate NK cytotoxicity through the NKG2D receptor.
Immunity. 2001 Feb;14(2):123-33 PMID: 11239445
The combined actions of NK and T lymphocytes are necessary to reject an EGFP+ mesenchymal tumor through mechanisms dependent on NKG2D and IFN gamma.
Int J Cancer. 2007 Sep 15;121(6):1282-95 PMID: 17520674
RNA interference targeting transforming growth factor-beta enhances NKG2D-mediated antiglioma immune response, inhibits glioma cell migration and invasiveness, and abrogates tumorigenicity in vivo.
Cancer Res. 2004 Oct 15;64(20):7596-603 PMID: 15492287
Cytotoxic T-lymphocyte-associated antigen-4.
Clin Cancer Res. 2007 Sep 15;13(18 Pt 1):5238-42 PMID: 17875750
The immunobiology of cancer immunosurveillance and immunoediting.
Immunity. 2004 Aug;21(2):137-48 PMID: 15308095
Incidence and prognostic impact of FoxP3+ regulatory T cells in human gliomas.
Clin Cancer Res. 2008 Aug 15;14(16):5166-72 PMID: 18698034
Sustained localized expression of ligand for the activating NKG2D receptor impairs natural cytotoxicity in vivo and reduces tumor immunosurveillance.
Nat Immunol. 2005 Sep;6(9):928-37 PMID: 16116470
A novel inhibitor of signal transducers and activators of transcription 3 activation is efficacious against established central nervous system melanoma and inhibits regulatory T cells.
Clin Cancer Res. 2008 Sep 15;14(18):5759-68 PMID: 18794085
Costimulation of CD8alphabeta T cells by NKG2D via engagement by MIC induced on virus-infected cells.
Nat Immunol. 2001 Mar;2(3):255-60 PMID: 11224526
Transforming growth factor beta 1 inhibits expression of NKp30 and NKG2D receptors: consequences for the NK-mediated killing of dendritic cells.
Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):4120-5 PMID: 12646700
Tumor development after 3-methylcholanthrene in immunologically deficient athymic-nude mice.
Science. 1974 Feb 8;183(4124):534-6 PMID: 4588620
Interleukin-15 rescues tolerant CD8+ T cells for use in adoptive immunotherapy of established tumors.
Nat Med. 2006 Mar;12(3):335-41 PMID: 16474399
Reduced natural killer (NK) function associated with high-risk myelodysplastic syndrome (MDS) and reduced expression of activating NK receptors.
Blood. 2007 Jun 1;109(11):4816-24 PMID: 17341666
Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA.
Science. 1999 Jul 30;285(5428):727-9 PMID: 10426993
Acute upregulation of an NKG2D ligand promotes rapid reorganization of a local immune compartment with pleiotropic effects on carcinogenesis.
Nat Immunol. 2008 Feb;9(2):146-54 PMID: 18176566
Interactions of human NKG2D with its ligands MICA, MICB, and homologs of the mouse RAE-1 protein family.
Immunogenetics. 2001 May-Jun;53(4):279-87 PMID: 11491531

Article Info

Journal

Neuro-oncology

Abbr.

Neuro Oncol

ISSN

1523-5866

DOI

10.1093/neuonc/nop009

Published

2010-01-00

Epub

2009-00-05

Pages

7-13

Language

English

Region

England

NLM ID

100887420

PMCID

PMC2940557

Subset

Grants

NCI NIH HHS · 2 P50 CA097257-06 · United States

NIAID NIH HHS · AI066897 · United States

External Links

PubMed source DOI: 10.1093/neuonc/nop009 PMC Full Text View journal details

Analysis Services

TGF-beta downregulates the activating receptor NKG2D on NK cells and CD8+ T cells in glioma patients.

Contact

WeChat Official Account