Immune evasion mediated by tumor-derived lactate dehydrogenase induction of NKG2D ligands on myeloid cells in glioblastoma patients
Abstract
This study describes a mechanism of immune escape in which glioblastoma cells produce a soluble protein, lactate dehydrogenase 5 (LDH5), that induces the expression of Natural killer group 2, member D (NKG2D) ligands on the surface of healthy myeloid cells. Expression of NKG2D ligands by myeloid cells causes the down-modulation of the activating NKG2D receptor on natural killer cells, thereby preventing their recognition of NKG2D ligand-bearing tumors and impairing their ability to attack and eliminate tumors. The discovery that monocytes in patients with several types of cancer also express NKG2D ligands suggests that LDH5 production by tumors may represent a common mechanism of immune evasion. Blocking LDH5 might improve recognition of tumors in cancer patients.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- September 2014
- DOI:
- 10.1073/pnas.1413933111
- Bibcode:
- 2014PNAS..11112823C