共 36 条
NK Cells Preferentially Target Tumor Cells with a Cancer Stem Cell Phenotype
被引:177
作者:

Ames, Erik
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Calif Davis, Sch Med, Dept Dermatol, Sacramento, CA 95817 USA Univ Calif Davis, Sch Med, Dept Dermatol, Sacramento, CA 95817 USA

Canter, Robert J.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Calif Davis, Sch Med, Dept Surg, Div Surg Oncol, Sacramento, CA 95817 USA Univ Calif Davis, Sch Med, Dept Dermatol, Sacramento, CA 95817 USA

Grossenbacher, Steven K.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Calif Davis, Sch Med, Dept Dermatol, Sacramento, CA 95817 USA Univ Calif Davis, Sch Med, Dept Dermatol, Sacramento, CA 95817 USA

Mac, Stephanie
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Calif Davis, Sch Med, Dept Dermatol, Sacramento, CA 95817 USA Univ Calif Davis, Sch Med, Dept Dermatol, Sacramento, CA 95817 USA

Chen, Mingyi
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Calif Davis, Sch Med, Dept Pathol & Lab Med, Sacramento, CA 95817 USA Univ Calif Davis, Sch Med, Dept Dermatol, Sacramento, CA 95817 USA

Smith, Rachel C.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Calif Davis, Sch Med, Dept Dermatol, Sacramento, CA 95817 USA Univ Calif Davis, Sch Med, Dept Dermatol, Sacramento, CA 95817 USA

Hagino, Takeshi
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Calif Davis, Sch Med, Dept Dermatol, Sacramento, CA 95817 USA Univ Calif Davis, Sch Med, Dept Dermatol, Sacramento, CA 95817 USA

Perez-Cunningham, Jessica
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Calif Davis, Sch Med, Dept Dermatol, Sacramento, CA 95817 USA Univ Calif Davis, Sch Med, Dept Dermatol, Sacramento, CA 95817 USA

Sckisel, Gail D.
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h-index: 0
机构:
Univ Calif Davis, Sch Med, Dept Dermatol, Sacramento, CA 95817 USA Univ Calif Davis, Sch Med, Dept Dermatol, Sacramento, CA 95817 USA

Urayama, Shiro
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Calif Davis, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol, Sacramento, CA 95817 USA Univ Calif Davis, Sch Med, Dept Dermatol, Sacramento, CA 95817 USA

Monjazeb, Arta M.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Calif Davis, Sch Med, Dept Radiat Oncol, Sacramento, CA 95817 USA Univ Calif Davis, Sch Med, Dept Dermatol, Sacramento, CA 95817 USA

Fragoso, Ruben C.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Calif Davis, Sch Med, Dept Radiat Oncol, Sacramento, CA 95817 USA Univ Calif Davis, Sch Med, Dept Dermatol, Sacramento, CA 95817 USA

Sayers, Thomas J.
论文数: 0 引用数: 0
h-index: 0
机构:
Leidos Biomedical Res Inc, Frederick Natl Lab, Basic Sci Program, Frederick, MD 21702 USA Univ Calif Davis, Sch Med, Dept Dermatol, Sacramento, CA 95817 USA

Murphy, William J.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Calif Davis, Sch Med, Dept Dermatol, Sacramento, CA 95817 USA
Univ Calif Davis, Med Ctr, Dept Internal Med, Div Hematol & Oncol, Sacramento, CA 95817 USA Univ Calif Davis, Sch Med, Dept Dermatol, Sacramento, CA 95817 USA
机构:
[1] Univ Calif Davis, Sch Med, Dept Dermatol, Sacramento, CA 95817 USA
[2] Univ Calif Davis, Sch Med, Dept Surg, Div Surg Oncol, Sacramento, CA 95817 USA
[3] Univ Calif Davis, Sch Med, Dept Pathol & Lab Med, Sacramento, CA 95817 USA
[4] Univ Calif Davis, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol, Sacramento, CA 95817 USA
[5] Univ Calif Davis, Sch Med, Dept Radiat Oncol, Sacramento, CA 95817 USA
[6] Leidos Biomedical Res Inc, Frederick Natl Lab, Basic Sci Program, Frederick, MD 21702 USA
[7] Univ Calif Davis, Med Ctr, Dept Internal Med, Div Hematol & Oncol, Sacramento, CA 95817 USA
基金:
美国国家卫生研究院;
关键词:
NATURAL-KILLER-CELLS;
GROWTH;
CYTOTOXICITY;
RECEPTORS;
LIGANDS;
D O I:
10.4049/jimmunol.1500447
中图分类号:
R392 [医学免疫学];
Q939.91 [免疫学];
学科分类号:
100102 ;
摘要:
Increasing evidence supports the hypothesis that cancer stem cells (CSCs) are resistant to antiproliferative therapies, able to repopulate tumor bulk, and seed metastasis. NK cells are able to target stem cells as shown by their ability to reject allogeneic hematopoietic stem cells but not solid tissue grafts. Using multiple preclinical models, including NK coculture (autologous and allogeneic) with multiple human cancer cell lines and dissociated primary cancer specimens and NK transfer in NSG mice harboring orthotopic pancreatic cancer xenografts, we assessed CSC viability, CSC frequency, expression of death receptor ligands, and tumor burden. We demonstrate that activated NK cells are capable of preferentially killing CSCs identified by multiple CSC markers (CD24(+)/CD44(+), CD133(+), and aldehyde dehydrogenase(bright)) from a wide variety of human cancer cell lines in vitro and dissociated primary cancer specimens ex vivo. We observed comparable effector function of allogeneic and autologous NK cells. We also observed preferential upregulation of NK activation ligands MICA/B, Fas, and DR5 on CSCs. Blocking studies further implicated an NKG2D-dependent mechanism for NK killing of CSCs. Treatment of orthotopic human pancreatic cancer tumor-bearing NSG mice with activated NK cells led to significant reductions in both intratumoral CSCs and tumor burden. Taken together, these data from multiple preclinical models, including a strong reliance on primary human cancer specimens, provide compelling preclinical evidence that activated NK cells preferentially target cancer cells with a CSC phenotype, highlighting the translational potential of NK immunotherapy as part of a combined modality approach for refractory solid malignancies.
引用
收藏
页码:4010 / 4019
页数:10
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;
Viens, Patrice
;
Birnbaum, Daniel
.
CANCER RESEARCH,
2013, 73 (24)
:7290-7300

Charafe-Jauffret, Emmanuelle
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CRCM, INSERM, U1068, F-13284 Marseille, France
Inst Paolicalmettes, F-13284 Marseille, France
Aix Marseille Univ, UM 105, F-13284 Marseille, France CRCM, INSERM, U1068, F-13284 Marseille, France

Ginestier, Christophe
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CRCM, INSERM, U1068, F-13284 Marseille, France CRCM, INSERM, U1068, F-13284 Marseille, France

Bertucci, Francois
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机构:
CRCM, INSERM, U1068, F-13284 Marseille, France
Aix Marseille Univ, UM 105, F-13284 Marseille, France
Inst Paolicalmettes, Dept Oncol Med, F-13284 Marseille, France CRCM, INSERM, U1068, F-13284 Marseille, France

Cabaud, Olivier
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CRCM, INSERM, U1068, F-13284 Marseille, France CRCM, INSERM, U1068, F-13284 Marseille, France

Wicinski, Julien
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CRCM, INSERM, U1068, F-13284 Marseille, France CRCM, INSERM, U1068, F-13284 Marseille, France

Finetti, Pascal
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CRCM, INSERM, U1068, F-13284 Marseille, France CRCM, INSERM, U1068, F-13284 Marseille, France

Josselin, Emmanuelle
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CRCM, INSERM, U1068, F-13284 Marseille, France CRCM, INSERM, U1068, F-13284 Marseille, France

Adelaide, Jose
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CRCM, INSERM, U1068, F-13284 Marseille, France CRCM, INSERM, U1068, F-13284 Marseille, France

Tien-Tuan Nguyen
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CRCM, INSERM, U1068, F-13284 Marseille, France CRCM, INSERM, U1068, F-13284 Marseille, France

Monville, Florence
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Jacquemier, Jocelyne
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Inst Paolicalmettes, F-13284 Marseille, France CRCM, INSERM, U1068, F-13284 Marseille, France

Thomassin-Piana, Jeanne
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Inst Paolicalmettes, F-13284 Marseille, France CRCM, INSERM, U1068, F-13284 Marseille, France

Pinna, Guillaume
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机构: CRCM, INSERM, U1068, F-13284 Marseille, France

Jalaguier, Aurelie
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机构:
Inst Paolicalmettes, Dept Radiol, F-13284 Marseille, France CRCM, INSERM, U1068, F-13284 Marseille, France

Lambaudie, Eric
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机构:
Inst Paolicalmettes, Dept Chirug Oncol, F-13284 Marseille, France CRCM, INSERM, U1068, F-13284 Marseille, France

Houvenaeghel, Gilles
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机构:
Aix Marseille Univ, UM 105, F-13284 Marseille, France
Inst Paolicalmettes, Dept Chirug Oncol, F-13284 Marseille, France CRCM, INSERM, U1068, F-13284 Marseille, France

Xerri, Luc
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Inst Paolicalmettes, F-13284 Marseille, France
Aix Marseille Univ, UM 105, F-13284 Marseille, France CRCM, INSERM, U1068, F-13284 Marseille, France

Harel-Bellan, Annick
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h-index: 0
机构:
CEA Saclay, Plateforme ARN interference PArI, F-91191 Gif Sur Yvette, France CRCM, INSERM, U1068, F-13284 Marseille, France

Chaffanet, Max
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CRCM, INSERM, U1068, F-13284 Marseille, France CRCM, INSERM, U1068, F-13284 Marseille, France

Viens, Patrice
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h-index: 0
机构:
CRCM, INSERM, U1068, F-13284 Marseille, France
Aix Marseille Univ, UM 105, F-13284 Marseille, France
Inst Paolicalmettes, Dept Oncol Med, F-13284 Marseille, France CRCM, INSERM, U1068, F-13284 Marseille, France

Birnbaum, Daniel
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h-index: 0
机构:
CRCM, INSERM, U1068, F-13284 Marseille, France CRCM, INSERM, U1068, F-13284 Marseille, France