Alternatively spliced NKp30 isoforms affect the prognosis of gastrointestinal stromal tumors

Nicolas F. Delahaye; Sylvie Rusakiewicz; Isabelle Martins; Cédric Ménard; Stephan Roux; Luc Lyonnet; Pascale Paul; Matthieu Sarabi; Nathalie Chaput; Michaela Semeraro; Véronique Minard-Colin; Vichnou Poirier-Colame; Kariman Chaba; Caroline Flament; Véronique Baud; Hélène Authier; Saadia Kerdine-Römer; Marc Pallardy; Isabelle Cremer; Laetitia Peaudecerf; Bénédita Rocha; Dominique Valteau-Couanet; Javier Celis Gutierrez; Jacques A. Nunès; Frédéric Commo; Sylvie Bonvalot; Nicolas Ibrahim; Philippe Terrier; Paule Opolon; Cristina Bottino; Alessandro Moretta; Jan Tavernier; Pascal Rihet; Jean Michel Coindre; Jean Yves Blay; Nicolas Isambert; Jean Franãois Emile; Eric Vivier; Axel Lecesne; Guido Kroemer; Laurence Zitvogel

doi:10.1038/nm.2366

Alternatively spliced NKp30 isoforms affect the prognosis of gastrointestinal stromal tumors

Nicolas F. Delahaye, Sylvie Rusakiewicz, Isabelle Martins, Cédric Ménard, Stephan Roux, Luc Lyonnet, Pascale Paul, Matthieu Sarabi, Nathalie Chaput, Michaela Semeraro, Véronique Minard-Colin, Vichnou Poirier-Colame, Kariman Chaba, Caroline Flament, Véronique Baud, Hélène Authier, Saadia Kerdine-Römer, Marc Pallardy, Isabelle Cremer, Laetitia PeaudecerfBénédita Rocha, Dominique Valteau-Couanet, Javier Celis Gutierrez, Jacques A. Nunès, Frédéric Commo, Sylvie Bonvalot, Nicolas Ibrahim, Philippe Terrier, Paule Opolon, Cristina Bottino, Alessandro Moretta, Jan Tavernier, Pascal Rihet, Jean Michel Coindre, Jean Yves Blay, Nicolas Isambert, Jean Franãois Emile, Eric Vivier, Axel Lecesne, Guido Kroemer, Laurence Zitvogel

Résultats de recherche: Contribution à un journal › Article › Revue par des pairs

280 Citations (Scopus)

Résumé

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-α (TNF-α) and CD107a release, and defective interferon- (IFN-) 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 3-2 untranslated region of the gene encoding NKp30. The genetically determined NKp30 status predicts the clinical outcomes of individuals with GIST independently from KIT mutation.

langue originale	Anglais
Pages (de - à)	700-707
Nombre de pages	8
journal	Nature Medicine
Volume	17
Numéro de publication	6
Les DOIs	https://doi.org/10.1038/nm.2366
état	Publié - 1 janv. 2011

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10.1038/nm.2366

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Delahaye, N. F., Rusakiewicz, S., Martins, I., Ménard, C., Roux, S., Lyonnet, L., Paul, P., Sarabi, M., Chaput, N., Semeraro, M., Minard-Colin, V., Poirier-Colame, V., Chaba, K., Flament, C., Baud, V., Authier, H., Kerdine-Römer, S., Pallardy, M., Cremer, I., ... Zitvogel, L. (2011). Alternatively spliced NKp30 isoforms affect the prognosis of gastrointestinal stromal tumors. Nature Medicine, 17(6), 700-707. https://doi.org/10.1038/nm.2366

@article{0438e5ab960e454db80b4522bca481b5,

title = "Alternatively spliced NKp30 isoforms affect the prognosis of gastrointestinal stromal tumors",

abstract = "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-α (TNF-α) and CD107a release, and defective interferon- (IFN-) 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 3-2 untranslated region of the gene encoding NKp30. The genetically determined NKp30 status predicts the clinical outcomes of individuals with GIST independently from KIT mutation.",

author = "Delahaye, {Nicolas F.} and Sylvie Rusakiewicz and Isabelle Martins and C{\'e}dric M{\'e}nard and Stephan Roux and Luc Lyonnet and Pascale Paul and Matthieu Sarabi and Nathalie Chaput and Michaela Semeraro and V{\'e}ronique Minard-Colin and Vichnou Poirier-Colame and Kariman Chaba and Caroline Flament and V{\'e}ronique Baud and H{\'e}l{\`e}ne Authier and Saadia Kerdine-R{\"o}mer and Marc Pallardy and Isabelle Cremer and Laetitia Peaudecerf and B{\'e}n{\'e}dita Rocha and Dominique Valteau-Couanet and Gutierrez, {Javier Celis} and Nun{\`e}s, {Jacques A.} and Fr{\'e}d{\'e}ric Commo and Sylvie Bonvalot and Nicolas Ibrahim and Philippe Terrier and Paule Opolon and Cristina Bottino and Alessandro Moretta and Jan Tavernier and Pascal Rihet and Coindre, {Jean Michel} and Blay, {Jean Yves} and Nicolas Isambert and Emile, {Jean Fran{\~a}ois} and Eric Vivier and Axel Lecesne and Guido Kroemer and Laurence Zitvogel",

note = "Funding Information: We thank P. Anderson for providing the CD3ζ-specific antibody (2H2 clone), M. Baratin for helpful discussions and the affected subjects as well as the healthy volunteers for their kind participation. U848 and U1015 are supported by Ligue contre le Cancer ({\'e}quipes labellis{\'e}es), Fondation pour la Recherche M{\'e}dicale, European Union (Apo-Sys, ArtForce, ChemoRes, INFLACARE), INCa ({\textquoteleft}NKp30{\textquoteright} in 2006; {\textquoteleft}NCR3 isoforms{\textquoteright} in 2008), Agence Nationale de la Recherche and Fondation de France (2009–2011). N.F.D. was supported by Institut National du Cancer and Fondation Gustave Roussy. S. Rusakiewicz was supported by a studentship from the Fondation pour la Recherche M{\'e}dicale. V.B. was supported by the Ligue contre le Cancer, Agence Nationale de la Recherche, Association pour la Recherche contre le Cancer, Belgian Interuniversity Attraction Pole, Canc{\'e}ropole Ile-de-France and Universit{\'e} Paris Descartes. J.C.G. was supported by the Fundayacucho-CNOUS joint program. Some materials and data used in this study were provided by the conticagist (https://www.conticagist.org/).",

year = "2011",

month = jan,

day = "1",

doi = "10.1038/nm.2366",

language = "English",

volume = "17",

pages = "700--707",

journal = "Nature Medicine",

issn = "1078-8956",

number = "6",

}

Delahaye, NF, Rusakiewicz, S, Martins, I, Ménard, C, Roux, S, Lyonnet, L, Paul, P, Sarabi, M, Chaput, N, Semeraro, M, Minard-Colin, V, Poirier-Colame, V, Chaba, K, Flament, C, Baud, V, Authier, H, Kerdine-Römer, S, Pallardy, M, Cremer, I, Peaudecerf, L, Rocha, B, Valteau-Couanet, D, Gutierrez, JC, Nunès, JA, Commo, F, Bonvalot, S, Ibrahim, N, Terrier, P, Opolon, P, Bottino, C, Moretta, A, Tavernier, J, Rihet, P, Coindre, JM, Blay, JY, Isambert, N, Emile, JF, Vivier, E, Lecesne, A, Kroemer, G & Zitvogel, L 2011, 'Alternatively spliced NKp30 isoforms affect the prognosis of gastrointestinal stromal tumors', Nature Medicine, VOL. 17, Numéro 6, p. 700-707. https://doi.org/10.1038/nm.2366

TY - JOUR

T1 - Alternatively spliced NKp30 isoforms affect the prognosis of gastrointestinal stromal tumors

AU - Delahaye, Nicolas F.

AU - Rusakiewicz, Sylvie

AU - Martins, Isabelle

AU - Ménard, Cédric

AU - Roux, Stephan

AU - Lyonnet, Luc

AU - Paul, Pascale

AU - Sarabi, Matthieu

AU - Chaput, Nathalie

AU - Semeraro, Michaela

AU - Minard-Colin, Véronique

AU - Poirier-Colame, Vichnou

AU - Chaba, Kariman

AU - Flament, Caroline

AU - Baud, Véronique

AU - Authier, Hélène

AU - Kerdine-Römer, Saadia

AU - Pallardy, Marc

AU - Cremer, Isabelle

AU - Peaudecerf, Laetitia

AU - Rocha, Bénédita

AU - Valteau-Couanet, Dominique

AU - Gutierrez, Javier Celis

AU - Nunès, Jacques A.

AU - Commo, Frédéric

AU - Bonvalot, Sylvie

AU - Ibrahim, Nicolas

AU - Terrier, Philippe

AU - Opolon, Paule

AU - Bottino, Cristina

AU - Moretta, Alessandro

AU - Tavernier, Jan

AU - Rihet, Pascal

AU - Coindre, Jean Michel

AU - Blay, Jean Yves

AU - Isambert, Nicolas

AU - Emile, Jean Franãois

AU - Vivier, Eric

AU - Lecesne, Axel

AU - Kroemer, Guido

AU - Zitvogel, Laurence

N1 - Funding Information: We thank P. Anderson for providing the CD3ζ-specific antibody (2H2 clone), M. Baratin for helpful discussions and the affected subjects as well as the healthy volunteers for their kind participation. U848 and U1015 are supported by Ligue contre le Cancer (équipes labellisées), Fondation pour la Recherche Médicale, European Union (Apo-Sys, ArtForce, ChemoRes, INFLACARE), INCa (‘NKp30’ in 2006; ‘NCR3 isoforms’ in 2008), Agence Nationale de la Recherche and Fondation de France (2009–2011). N.F.D. was supported by Institut National du Cancer and Fondation Gustave Roussy. S. Rusakiewicz was supported by a studentship from the Fondation pour la Recherche Médicale. V.B. was supported by the Ligue contre le Cancer, Agence Nationale de la Recherche, Association pour la Recherche contre le Cancer, Belgian Interuniversity Attraction Pole, Cancéropole Ile-de-France and Université Paris Descartes. J.C.G. was supported by the Fundayacucho-CNOUS joint program. Some materials and data used in this study were provided by the conticagist (https://www.conticagist.org/).

PY - 2011/1/1

Y1 - 2011/1/1

N2 - 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-α (TNF-α) and CD107a release, and defective interferon- (IFN-) 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 3-2 untranslated region of the gene encoding NKp30. The genetically determined NKp30 status predicts the clinical outcomes of individuals with GIST independently from KIT mutation.

AB - 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-α (TNF-α) and CD107a release, and defective interferon- (IFN-) 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 3-2 untranslated region of the gene encoding NKp30. The genetically determined NKp30 status predicts the clinical outcomes of individuals with GIST independently from KIT mutation.

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U2 - 10.1038/nm.2366

DO - 10.1038/nm.2366

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JO - Nature Medicine

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