共 35 条
Tumor-mediated liver X receptor-α activation inhibits CC chemokine receptor-7 expression on dendritic cells and dampens antitumor responses
被引:260
作者:

Villablanca, Eduardo J.
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机构:
Ist Sci San Raffaele, Div Mol Oncol, Program Immunol & Bio Immuno Gene Therapy Canc, Canc Gene Therapy Unit, I-20132 Milan, Italy
Univ Vita Salute San Raffaele, Milan, Italy Ist Sci San Raffaele, Div Mol Oncol, Program Immunol & Bio Immuno Gene Therapy Canc, Canc Gene Therapy Unit, I-20132 Milan, Italy

Raccosta, Laura
论文数: 0 引用数: 0
h-index: 0
机构:
Ist Sci San Raffaele, Div Mol Oncol, Program Immunol & Bio Immuno Gene Therapy Canc, Canc Gene Therapy Unit, I-20132 Milan, Italy Ist Sci San Raffaele, Div Mol Oncol, Program Immunol & Bio Immuno Gene Therapy Canc, Canc Gene Therapy Unit, I-20132 Milan, Italy

Zhou, Dan
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h-index: 0
机构:
MolMed SpA, Milan, Italy Ist Sci San Raffaele, Div Mol Oncol, Program Immunol & Bio Immuno Gene Therapy Canc, Canc Gene Therapy Unit, I-20132 Milan, Italy

Fontana, Raffaella
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h-index: 0
机构:
Ist Sci San Raffaele, Div Mol Oncol, Program Immunol & Bio Immuno Gene Therapy Canc, Canc Gene Therapy Unit, I-20132 Milan, Italy Ist Sci San Raffaele, Div Mol Oncol, Program Immunol & Bio Immuno Gene Therapy Canc, Canc Gene Therapy Unit, I-20132 Milan, Italy

Maggioni, Daniela
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机构:
Ist Sci San Raffaele, Div Mol Oncol, Program Immunol & Bio Immuno Gene Therapy Canc, Canc Gene Therapy Unit, I-20132 Milan, Italy Ist Sci San Raffaele, Div Mol Oncol, Program Immunol & Bio Immuno Gene Therapy Canc, Canc Gene Therapy Unit, I-20132 Milan, Italy

Negro, Aurora
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机构:
Ist Sci San Raffaele, Div Mol Oncol, Program Immunol & Bio Immuno Gene Therapy Canc, Canc Gene Therapy Unit, I-20132 Milan, Italy Ist Sci San Raffaele, Div Mol Oncol, Program Immunol & Bio Immuno Gene Therapy Canc, Canc Gene Therapy Unit, I-20132 Milan, Italy

Sanvito, Francesca
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h-index: 0
机构:
Ist Sci San Raffaele, Dept Pathol, I-20132 Milan, Italy Ist Sci San Raffaele, Div Mol Oncol, Program Immunol & Bio Immuno Gene Therapy Canc, Canc Gene Therapy Unit, I-20132 Milan, Italy

Ponzoni, Maurilio
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h-index: 0
机构:
Ist Sci San Raffaele, Dept Pathol, I-20132 Milan, Italy Ist Sci San Raffaele, Div Mol Oncol, Program Immunol & Bio Immuno Gene Therapy Canc, Canc Gene Therapy Unit, I-20132 Milan, Italy

Valentinis, Barbara
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h-index: 0
机构:
MolMed SpA, Milan, Italy Ist Sci San Raffaele, Div Mol Oncol, Program Immunol & Bio Immuno Gene Therapy Canc, Canc Gene Therapy Unit, I-20132 Milan, Italy

Bregni, Marco
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h-index: 0
机构:
Ist Sci San Raffaele, Strateg Program Oncol, I-20132 Milan, Italy Ist Sci San Raffaele, Div Mol Oncol, Program Immunol & Bio Immuno Gene Therapy Canc, Canc Gene Therapy Unit, I-20132 Milan, Italy

Prinetti, Alessandro
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h-index: 0
机构:
Univ Milan, Dept Med Chem Biochem & Biotechnol, Ctr Excellence Neurodegenerat Dis, Segrate, Italy Ist Sci San Raffaele, Div Mol Oncol, Program Immunol & Bio Immuno Gene Therapy Canc, Canc Gene Therapy Unit, I-20132 Milan, Italy

Steffensen, Knut R.
论文数: 0 引用数: 0
h-index: 0
机构:
Karolinska Inst, Novum, Dept Biosci & Nutr, Huddinge, Sweden Ist Sci San Raffaele, Div Mol Oncol, Program Immunol & Bio Immuno Gene Therapy Canc, Canc Gene Therapy Unit, I-20132 Milan, Italy

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Gustafsson, Jan-Ake
论文数: 0 引用数: 0
h-index: 0
机构:
Karolinska Inst, Novum, Dept Biosci & Nutr, Huddinge, Sweden
Univ Houston, Ctr Nucl Receptors & Cell Signaling, Houston, TX USA Ist Sci San Raffaele, Div Mol Oncol, Program Immunol & Bio Immuno Gene Therapy Canc, Canc Gene Therapy Unit, I-20132 Milan, Italy

Doglioni, Claudio
论文数: 0 引用数: 0
h-index: 0
机构:
Ist Sci San Raffaele, Dept Pathol, I-20132 Milan, Italy Ist Sci San Raffaele, Div Mol Oncol, Program Immunol & Bio Immuno Gene Therapy Canc, Canc Gene Therapy Unit, I-20132 Milan, Italy

Bordignon, Claudio
论文数: 0 引用数: 0
h-index: 0
机构:
Ist Sci San Raffaele, Div Mol Oncol, Program Immunol & Bio Immuno Gene Therapy Canc, Canc Gene Therapy Unit, I-20132 Milan, Italy
MolMed SpA, Milan, Italy Ist Sci San Raffaele, Div Mol Oncol, Program Immunol & Bio Immuno Gene Therapy Canc, Canc Gene Therapy Unit, I-20132 Milan, Italy

Traversari, Catia
论文数: 0 引用数: 0
h-index: 0
机构:
MolMed SpA, Milan, Italy Ist Sci San Raffaele, Div Mol Oncol, Program Immunol & Bio Immuno Gene Therapy Canc, Canc Gene Therapy Unit, I-20132 Milan, Italy

Russo, Vincenzo
论文数: 0 引用数: 0
h-index: 0
机构:
Ist Sci San Raffaele, Div Mol Oncol, Program Immunol & Bio Immuno Gene Therapy Canc, Canc Gene Therapy Unit, I-20132 Milan, Italy Ist Sci San Raffaele, Div Mol Oncol, Program Immunol & Bio Immuno Gene Therapy Canc, Canc Gene Therapy Unit, I-20132 Milan, Italy
机构:
[1] Ist Sci San Raffaele, Div Mol Oncol, Program Immunol & Bio Immuno Gene Therapy Canc, Canc Gene Therapy Unit, I-20132 Milan, Italy
[2] Univ Vita Salute San Raffaele, Milan, Italy
[3] MolMed SpA, Milan, Italy
[4] Ist Sci San Raffaele, Dept Pathol, I-20132 Milan, Italy
[5] Ist Sci San Raffaele, Strateg Program Oncol, I-20132 Milan, Italy
[6] Univ Milan, Dept Med Chem Biochem & Biotechnol, Ctr Excellence Neurodegenerat Dis, Segrate, Italy
[7] Karolinska Inst, Novum, Dept Biosci & Nutr, Huddinge, Sweden
[8] Univ Houston, Ctr Nucl Receptors & Cell Signaling, Houston, TX USA
关键词:
NUCLEAR RECEPTORS;
T-CELLS;
MIGRATION;
METABOLISM;
CHOLESTEROL;
IMMUNOGENICITY;
INFLAMMATION;
OXYSTEROLS;
DEPLETION;
THERAPY;
D O I:
10.1038/nm.2074
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
Sterol metabolism has recently been linked to innate and adaptive immune responses through liver X receptor (LXR) signaling. Whether products of sterol metabolism interfere with antitumor responses is currently unknown. Dendritic cells (DCs) initiate immune responses, including antitumor activity after their CC chemokine receptor-7 (CCR7)-dependent migration to lymphoid organs. Here we report that human and mouse tumors produce LXR ligands that inhibit CCR7 expression on maturing DCs and, therefore, their migration to lymphoid organs. In agreement with this observation, we detected CD83(+)CCR7(-) DCs within human tumors. Mice injected with tumors expressing the LXR ligand-inactivating enzyme sulfotransferase 2B1b (SULT2B1b) successfully controlled tumor growth by regaining DC migration to tumor-draining lymph nodes and by developing overt inflammation within tumors. The control of tumor growth was also observed in chimeric mice transplanted with bone marrow from mice lacking the gene encoding LXR-alpha (Nr1h3(-/-) mice) Thus, we show a new mechanism of tumor immunoescape involving products of cholesterol metabolism. The manipulation of this pathway could restore antitumor immunity in individuals with cancer.
引用
收藏
页码:98 / U137
页数:9
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Capuano, Giusy
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Jachetti, Elena
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Freschi, Massimo
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Bertilaccio, Maria T. S.
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Hess-Michelini, Rodrigo
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Doglioni, Claudio
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Bellone, Matteo
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[10]
Oxysterols are substrates for cholesterol sulfotransferase
[J].
Fuda, Hirotoshi
;
Javitt, Normal B.
;
Mitamura, Kuniko
;
Ikegawa, Shigeo
;
Strott, Charles A.
.
JOURNAL OF LIPID RESEARCH,
2007, 48 (06)
:1343-1352

Fuda, Hirotoshi
论文数: 0 引用数: 0
h-index: 0
机构: NICHHD, Sect Steroid Regulat, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA

Javitt, Normal B.
论文数: 0 引用数: 0
h-index: 0
机构: NICHHD, Sect Steroid Regulat, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA

Mitamura, Kuniko
论文数: 0 引用数: 0
h-index: 0
机构: NICHHD, Sect Steroid Regulat, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA

Ikegawa, Shigeo
论文数: 0 引用数: 0
h-index: 0
机构: NICHHD, Sect Steroid Regulat, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA

Strott, Charles A.
论文数: 0 引用数: 0
h-index: 0
机构:
NICHHD, Sect Steroid Regulat, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA NICHHD, Sect Steroid Regulat, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA