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Immune evasion mediated by tumor-derived lactate dehydrogenase induction of NKG2D ligands on myeloid cells in glioblastoma patients.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2014 Sep 02; Vol. 111 (35), pp. 12823-8. Date of Electronic Publication: 2014 Aug 18. - Publication Year :
- 2014
-
Abstract
- Myeloid cells are key regulators of the tumor microenvironment, governing local immune responses. Here we report that tumor-infiltrating myeloid cells and circulating monocytes in patients with glioblastoma multiforme (GBM) express ligands for activating the Natural killer group 2, member D (NKG2D) receptor, which cause down-regulation of NKG2D on natural killer (NK) cells. Tumor-infiltrating NK cells isolated from GBM patients fail to lyse NKG2D ligand-expressing tumor cells. We demonstrate that lactate dehydrogenase (LDH) isoform 5 secreted by glioblastoma cells induces NKG2D ligands on monocytes isolated from healthy individuals. Furthermore, sera from GBM patients contain elevated amounts of LDH, which correlate with expression of NKG2D ligands on their autologous circulating monocytes. NKG2D ligands also are present on circulating monocytes isolated from patients with breast, prostate, and hepatitis C virus-induced hepatocellular carcinomas. Together, these findings reveal a previously unidentified immune evasion strategy whereby tumors produce soluble factors that induce NKG2D ligands on myeloid cells, subverting antitumor immune responses.
- Subjects :
- Cell Line, Tumor
GPI-Linked Proteins immunology
Glioma immunology
HEK293 Cells
Histocompatibility Antigens Class I immunology
Humans
Immunity, Innate immunology
Intracellular Signaling Peptides and Proteins immunology
Isoenzymes immunology
Killer Cells, Natural cytology
Killer Cells, Natural immunology
Lactate Dehydrogenase 5
Monocytes cytology
Monocytes immunology
Myeloid Cells cytology
Myeloid Cells immunology
Brain Neoplasms immunology
Glioblastoma immunology
Immune Evasion immunology
L-Lactate Dehydrogenase immunology
NK Cell Lectin-Like Receptor Subfamily K immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 111
- Issue :
- 35
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 25136121
- Full Text :
- https://doi.org/10.1073/pnas.1413933111