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Journal articles
NKG2D controls natural reactivity of Vγ9Vδ2 T lymphocytes against mesenchymal glioblastoma cells: Vγ9Vδ2 T lymphocytes react against mesenchymal glioblastoma
Cynthia Chauvin
1, 2
Noémie Joalland
3, 2
Jeanne Perroteau
3, 2
Ulrich Jarry
3, 2
Laura Lafrance
3, 2
Catherine Willem
3, 4
Christelle Retiere
3
Lisa Oliver
1
Catherine Gratas
5
Laetitia Gautreau-Rolland
3, 2
Xavier Saulquin
3, 2
François Vallette
1, 2, 6
Henri Vié
3, 2
Emmanuel Scotet
3, 2
Claire Pecqueur
5, 2, *
*
Corresponding author
1
CRCINA-ÉQUIPE 9 - Apoptosis and Tumor Progression
CRCINA - Centre de Recherche en Cancérologie et Immunologie Nantes-Angers
3
CRCINA-ÉQUIPE 1 - Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications
CRCINA - Centre de Recherche en Cancérologie et Immunologie Nantes-Angers
5
CRCINA-ÉQUIPE 14 - Endothelium Radiobiology and Targeting
CRCINA - Centre de Recherche en Cancérologie et Immunologie Nantes-Angers
Cynthia Chauvin 1, 2
Author
Noémie Joalland 3, 2
Author
Jeanne Perroteau 3, 2
Author
Ulrich Jarry 3, 2
Author
Laura Lafrance 3, 2
Author
Catherine Willem 3, 4
Author
Christelle Retiere 3
Author
Lisa M Oliver 1
Author
Catherine Gratas 5
Author
Laetitia Gautreau-Rolland 3, 2
Author
Xavier Saulquin 3, 2
Mail :
Author
François M Vallette 1, 2, 6
Author
Henri Vié 3, 2
Author
Emmanuel Scotet 3, 2
Mail :
Author IdHAL : emmanuel-scotet ORCID : https://orcid.org/0000-0001-8010-9556
Claire Pecqueur 5, 2
Mail :
Correspondent author IdHAL : clairepecqueur ORCID : https://orcid.org/0000-0002-7612-1672
1
CRCINA-ÉQUIPE 9 - Apoptosis and Tumor Progression (Institut de Recherche en Santé de l'Université de Nantes - 8 quai Moncousu - BP 70721 - 44007 Nantes cedex 1 - France)
- CRCINA - Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (8 quai de Moncousu - BP 70721 - 44007 Nantes Cedex 1 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : UMR1232 (101, rue de Tolbiac, 75013 Paris - France)
- UFR MEDECINE - Université de Nantes - UFR de Médecine et des Techniques Médicales : UMR1232 (1 rue Gaston Veil BP 53508 44035 NANTES Cedex 1 - France)
- UN - Université de Nantes (1, quai de Tourville - BP 13522 - 44035 Nantes cedex 1 - France)
- CHU Nantes - Centre hospitalier universitaire de Nantes : UMR1232 (1 Place Alexis-Ricordeau, 44000 Nantes - France)
- CNRS - Centre National de la Recherche Scientifique : ERL6001 (France)
- UA - Université d'Angers : UMR1232 (Université d'Angers - 40 Rue de Rennes, BP 73532 - 49035 Angers CEDEX 01 - France)
2
LabEX IGO Immunothérapie Grand Ouest (France)
3
CRCINA-ÉQUIPE 1 - Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (Institut de Recherche en Santé de l'Université de Nantes - 8 quai Moncousu - BP 70721 - 44007 Nantes cedex 1 - France)
- CRCINA - Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (8 quai de Moncousu - BP 70721 - 44007 Nantes Cedex 1 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : UMR1232 (101, rue de Tolbiac, 75013 Paris - France)
- UFR MEDECINE - Université de Nantes - UFR de Médecine et des Techniques Médicales : UMR1232 (1 rue Gaston Veil BP 53508 44035 NANTES Cedex 1 - France)
- UN - Université de Nantes (1, quai de Tourville - BP 13522 - 44035 Nantes cedex 1 - France)
- CHU Nantes - Centre hospitalier universitaire de Nantes : UMR1232 (1 Place Alexis-Ricordeau, 44000 Nantes - France)
- CNRS - Centre National de la Recherche Scientifique : ERL6001 (France)
- UA - Université d'Angers : UMR1232 (Université d'Angers - 40 Rue de Rennes, BP 73532 - 49035 Angers CEDEX 01 - France)
4
Etablissement Français du Sang [Nantes] (34 bd Jean-Monnet
44000 - Nantes - France)
5
CRCINA-ÉQUIPE 14 - Endothelium Radiobiology and Targeting (Institut de Recherche en Santé de l'Université de Nantes - 8 quai Moncousu - BP 70721 - 44007 Nantes cedex 1 - France)
- CRCINA - Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (8 quai de Moncousu - BP 70721 - 44007 Nantes Cedex 1 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : UMR1232 (101, rue de Tolbiac, 75013 Paris - France)
- UFR MEDECINE - Université de Nantes - UFR de Médecine et des Techniques Médicales : UMR1232 (1 rue Gaston Veil BP 53508 44035 NANTES Cedex 1 - France)
- UN - Université de Nantes (1, quai de Tourville - BP 13522 - 44035 Nantes cedex 1 - France)
- CHU Nantes - Centre hospitalier universitaire de Nantes : UMR1232 (1 Place Alexis-Ricordeau, 44000 Nantes - France)
- CNRS - Centre National de la Recherche Scientifique : ERL6001 (France)
- UA - Université d'Angers : UMR1232 (Université d'Angers - 40 Rue de Rennes, BP 73532 - 49035 Angers CEDEX 01 - France)
6
UNICANCER/ICO - Institut de Cancérologie de l'Ouest [Angers/Nantes] (15, rue André Boquel - 49055 Angers cedex 02 - France)
- UNICANCER (101, rue de Tolbiac, 75654 Paris Cedex 13 - France)
Abstract : PURPOSE:
Cellular immunotherapies are currently being explored to eliminate highly invasive and chemoradioresistant glioblastoma (GBM) cells involved in rapid relapse. We recently showed that concomitant stereotactic injections of non-alloreactive allogeneic Vγ9Vδ2 T lymphocytes eradicate zoledronate-primed human GBM cells. In the present study, we investigated the spontaneous reactivity of allogeneic human Vγ9Vδ2 T lymphocytes toward primary human GBM cells, in vitro and in vivo, in absence of any prior sensitization.
EXPERIMENTAL DESIGN:
Through functional and trancriptomic analyses, we extensively characterized the immunoreactivity of human Vγ9Vδ2 T lymphocytes against various primary GBM cultures directly derived from patient tumors.
RESULTS:
We evidence that GBM cells displaying a mesenchymal subtype signature are spontaneously eliminated by allogeneic human Vγ9Vδ2 T lymphocytes, a reactivity process being mediated by γδ TCR and tightly regulated by cellular stress-associated NKG2D pathway. This led to the identification of highly-reactive Vγ9Vδ2 T lymphocyte populations, independently of a specific TCR repertoire signature. Moreover, we finally provide evidence of immunotherapeutic efficacy in vivo, in absence of any prior tumor cell sensitization.
CONCLUSIONS:
By identifying pathways implicated in the selective natural recognition of mesenchymal GBM cell subtypes, accounting for 30% of primary diagnosed and 60% of recurrent GBM, our results pave the way for novel targeted cellular immunotherapies.
Copyright ©2019, American Association for Cancer Research.
Document type :
Journal articles
Domain :
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https://www.hal.inserm.fr/inserm-02316604
Contributor : Elizabeth Bernardo <>
Submitted on : Tuesday, October 15, 2019 - 2:16:53 PM
Last modification on : Friday, June 19, 2020 - 1:40:17 AM
Document(s) archivé(s) le : Friday, January 17, 2020 - 2:13:56 PM
Contributor : Elizabeth Bernardo <>
Submitted on : Tuesday, October 15, 2019 - 2:16:53 PM
Last modification on : Friday, June 19, 2020 - 1:40:17 AM
Document(s) archivé(s) le : Friday, January 17, 2020 - 2:13:56 PM
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Identifiers
- HAL Id : inserm-02316604, version 1
- DOI : 10.1158/1078-0432.CCR-19-0375
- PUBMED : 31506386
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CNRS | CRCINA | UNIV-NANTES | UNIV-ANGERS
Citation
Cynthia Chauvin, Noémie Joalland, Jeanne Perroteau, Ulrich Jarry, Laura Lafrance, et al.. NKG2D controls natural reactivity of Vγ9Vδ2 T lymphocytes against mesenchymal glioblastoma cells: Vγ9Vδ2 T lymphocytes react against mesenchymal glioblastoma. Clinical Cancer Research, American Association for Cancer Research, In press, clincanres.0375.2019 (Epub ahead of print). ⟨10.1158/1078-0432.CCR-19-0375⟩. ⟨inserm-02316604⟩
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