Journal
NATURE MEDICINE
Volume 18, Issue 12, Pages 1827-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.3013
Keywords
-
Funding
- US National Institutes of Health [7U01NS061811, CA069246, CA068458, CA095426, TL1RR025753, CA163205]
- American Medical Association Foundation Seed Grant
- Dardinger Neuro-oncology Laboratory
Ask authors/readers for more resources
The role of the immune response to oncolytic Herpes simplex viral (oHSV) therapy for glioblastoma is controversial because it might enhance or inhibit efficacy. We found that within hours of oHSV infection of glioblastomas in mice, activated natural killer (NK) cells are recruited to the site of infection. This response substantially diminished the efficacy of glioblastoma virotherapy. oHSV-activated NK cells coordinated macrophage and microglia activation within tumors. In vitro, human NK cells preferentially lysed oHSV-infected human glioblastoma cell lines. This enhanced killing depended on the NK cell natural cytotoxicity receptors (NCRs) NKp30 and NKp46, whose ligands are upregulated in oHSV-infected glioblastoma cells. We found that HSV titers and oHSV efficacy are increased in Ncr1(-/-) mice and a Ncr1(-/-) NK cell adoptive transfer model of glioma, respectively. These results demonstrate that glioblastoma virotherapy is limited partially by an antiviral NK cell response involving specific NCRs, uncovering new potential targets to enhance cancer virotherapy.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available