Alternatively spliced NKp30 isoforms affect the prognosis of gastrointestinal stromal tumors

被引：281

作者：

Delahaye, Nicolas F. ^{[1
,2
]}

Rusakiewicz, Sylvie ^{[1
,2
]}

Martins, Isabelle ^{[3
,4
]}

Menard, Cedric ^{[1
,2
]}

Roux, Stephan ^{[1
,2
]}

Lyonnet, Luc ^{[5
]}

Paul, Pascale ^{[5
]}

Sarabi, Matthieu ^{[1
,2
]}

Chaput, Nathalie ^{[1
,2
]}

Semeraro, Michaela ^{[1
,6
]}

Minard-Colin, Veronique ^{[1
,6
]}

Poirier-Colame, Vichnou ^{[2
]}

Chaba, Kariman ^{[1
]}

Flament, Caroline ^{[1
,2
]}

Baud, Veronique ^{[3
,7
,8
]}

Authier, Helene ^{[3
,7
,8
]}

Kerdine-Roemer, Saadia ^{[9
]}

Pallardy, Marc ^{[9
]}

Cremer, Isabelle ^{[10
,11
]}

Peaudecerf, Laetitia ^{[12
,13
]}

Rocha, Benedita ^{[12
,13
]}

Valteau-Couanet, Dominique ^{[1
,6
]}

Gutierrez, Javier Celis ^{[14
,15
]}

Nunes, Jacques A. ^{[14
,15
]}

Commo, Frederic ^{[16
]}

Bonvalot, Sylvie ^{[17
]}

Ibrahim, Nicolas ^{[18
]}

Terrier, Philippe ^{[17
,18
]}

Opolon, Paule ^{[19
,20
]}

Bottino, Cristina ^{[21
,22
]}

Moretta, Alessandro ^{[21
]}

Tavernier, Jan ^{[23
,24
]}

Rihet, Pascal ^{[25
]}

Coindre, Jean-Michel ^{[26
]}

Blay, Jean-Yves ^{[27
]}

Isambert, Nicolas ^{[28
,29
]}

Emile, Jean-Francois ^{[30
]}

Vivier, Eric ^{[31
,32
,33
,34
]}

Lecesne, Axel ^{[2
,17
]}

Kroemer, Guido ^{[3
,4
,35
,36
]}

Zitvogel, Laurence ^{[1
,2
]}

机构：

[1] IGR, INSERM, U1015, Villejuif, France

[2] IGR, Ctr Clin Invest CBT507, Villejuif, France

[3] Univ Paris 05, Paris, France

[4] IGR, INSERM, U848, Villejuif, France

[5] Hop Conception, Hematol Unit, Marseille, France

[6] IGR, Dept Pediat Oncol, Villejuif, France

[7] Inst Cochin, INSERM, U1016, Paris, France

[8] CNRS, UMR8104, Paris, France

[9] Universud, INSERM, Fac Pharm, UMR 996, Chatenay Malabry, France

[10] Ctr Rech Cordeliers, INSERM, U872, Paris, France

[11] Univ Paris 06, UMRS 872, Paris, France

[12] INSERM, U1020, Paris, France

[13] Fac Med Rene Descartes, Paris, France

[14] Ctr Rech Cancerol Marseille, INSERM, U891, Marseille, France

[15] Inst J Paoli I Calmettes, F-13009 Marseille, France

[16] IGR, INSERM, U981, Villejuif, France

[17] IGR, Dept Med, Sarcoma Comm, Villejuif, France

[18] IGR, Dept Pathol, Villejuif, France

[19] IGR, Expt Pathol Unit, Villejuif, France

[20] Univ Paris 11, Fac Med Paris Sud, Le Kremlin Bicetre, France

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

[22] Ist Giannina Gaslini, I-16148 Genoa, Italy

[23] Univ Ghent, Fac Med & Hlth, Dept Med Prot Res, B-9000 Ghent, Belgium

[24] Univ Ghent VIB, Ghent, Belgium

[25] Aix Marseille Univ, INSERM, TAGC, U928, Marseille, France

[26] Inst Bergonie, Dept Pathol, Bordeaux, France

[27] Ctr Leon Berard, Dept Med, F-69373 Lyon, France

[28] Ctr Georges Francois Leclerc, Dept Oncol, Dijon, France

[29] INSERM, CIC P 803, Dijon, France

[30] Hop Ambroise Pare, Dept Pathol, EA4340, Boulogne, France

[31] Univ Aix Marseille 2, Ctr Immunol Marseille Luminy, Marseille, France

[32] INSERM, U631, F-13258 Marseille, France

[33] CNRS, UniteMixte Rech 6102, Marseille, France

[34] Hop Conception, AP HM, Marseille, France

[35] Ctr Rech Cordeliers, Paris, France

[36] Hop Europeen Georges Pompidou, AP HP, Paris, France

来源：

NATURE MEDICINE | 2011年 / 17卷 / 06期

关键词：

NATURAL-KILLER-CELLS; HUMAN DENDRITIC CELLS; NK CELLS; HUMAN MHC; CYTOTOXICITY RECEPTORS; TRIGGERING RECEPTOR; IL-10; PRODUCTION; CLASS-III; C-KIT; EXPRESSION;

D O I：

10.1038/nm.2366

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：

The natural killer (NK) cell receptor NKp30 is involved in the recognition of tumor and dendritic cells (DCs). Here we describe the influence of three NKp30 splice variants on the prognosis of gastrointestinal sarcoma (GIST), a malignancy that expresses NKp30 ligands and that is treated with NK-stimulatory KIT tyrosine kinase inhibitors. Healthy individuals and those with GIST show distinct patterns of transcription of functionally different NKp30 isoforms. In a retrospective analysis of 80 individuals with GIST, predominant expression of the immunosuppressive NKp30c isoform (over the immunostimulatory NKp30a and NKp30b isoforms) was associated with reduced survival of subjects, decreased NKp30-dependent tumor necrosis factor-alpha (TNF-alpha) and CD107a release, and defective interferon-gamma (IFN-gamma) and interleukin-12 (IL-12) secretion in the NK-DC cross-talk that could be restored by blocking of IL-10. Preferential NKp30c expression resulted partly from a single-nucleotide polymorphism at position 3790 in the 3' untranslated region of the gene encoding NKp30. The genetically determined NKp30 status predicts the clinical outcomes of individuals with GIST independently from KIT mutation.

引用

页码：700 / +

页数：9

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