NK cells impede glioblastoma virotherapy through NKp30 and NKp46 natural cytotoxicity receptors

被引：170

作者：

Alvarez-Breckenridge, Christopher A. ^{[1
,2
,3
,4
]}

Yu, Jianhua ^{[2
,3
,5
,6
]}

Price, Richard ^{[1
,2
,3
,4
]}

Wojton, Jeffrey ^{[1
,2
,3
]}

Pradarelli, Jason ^{[1
,2
,3
]}

Mao, Hsiaoyin ^{[2
,3
,6
]}

Wei, Min ^{[2
,3
,6
]}

Wang, Yan ^{[1
,2
,3
]}

He, Shun ^{[2
,3
,6
]}

Hardcastle, Jayson ^{[1
,2
,3
]}

Fernandez, Soledad A. ^{[2
,3
,6
,7
]}

Kaur, Balveen ^{[1
,2
,3
,6
]}

Lawler, Sean E. ^{[1
,2
,3
]}

Vivier, Eric ^{[8
]}

Mandelboim, Ofer ^{[9
]}

Moretta, Alessandro ^{[10
,11
]}

Caligiuri, Michael A. ^{[2
,3
,5
,6
]}

Chiocca, E. Antonio ^{[1
,2
,3
,6
,12
]}

机构：

[1] Ohio State Univ, Med Ctr, Dept Neurol Surg, Dardinger Lab Neurooncol & Neurosci, Columbus, OH 43210 USA

[2] James Canc Hosp, Columbus, OH USA

[3] Solove Res Inst, Columbus, OH USA

[4] Ohio State Univ, Med Ctr, Med Scientist Training Program, Columbus, OH 43210 USA

[5] Ohio State Univ, Med Ctr, Div Hematol, Columbus, OH 43210 USA

[6] Ohio State Univ, Med Ctr, Ctr Comprehens Canc, Columbus, OH 43210 USA

[7] Ohio State Univ, Med Ctr, Ctr Biostat, Columbus, OH 43210 USA

[8] Univ Aix Marseille 2, INSERM, U631, Ctr Immunol Marseille Luminy, Marseille, France

[9] Hebrew Univ Jerusalem, Hadassah Med Sch, Lautenberg Ctr Gen & Tumor Immunol, Inst Med Res Israel Canada, IL-91010 Jerusalem, Israel

[10] Univ Genoa, Dipartimento Med Sperimentale, Genoa, Italy

[11] Univ Genoa, Ctr Eccellenza Ric Biomed, Genoa, Italy

[12] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Sch Med,Dept Neurosurg, Boston, MA 02115 USA

来源：

NATURE MEDICINE | 2012年 / 18卷 / 12期

基金：

美国国家卫生研究院;

关键词：

HERPES-SIMPLEX-VIRUS; VESICULAR STOMATITIS-VIRUS; HUMAN DENDRITIC CELLS; KILLER-CELLS; TUMOR MICROENVIRONMENT; DEPENDENT MECHANISMS; TRIGGERING RECEPTOR; GLIOMA VIROTHERAPY; ONCOLYTIC VIRUSES; IMMUNE-RESPONSES;

D O I：

10.1038/nm.3013

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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.

引用

页码：1827 / +

页数：10

共 61 条

[1]

Oncolytic herpes virus with defective ICP6 specifically replicates in quiescent cells with homozygous genetic mutations in p16 [J].