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Oncoimmunology. 2017 Sep 21;7(1):e1372080. doi: 10.1080/2162402X.2017.1372080. eCollection 2017.

BTN3A is a prognosis marker and a promising target for Vγ9Vδ2 T cells based-immunotherapy in pancreatic ductal adenocarcinoma (PDAC).

Author information

1
Inserm, U1068, Centre de Recherche en Cancérologie de Marseille (CRCM), Immunity & Cancer, Institut Paoli-Calmettes; Aix-Marseille Université UM 105; CNRS UMR 7258, Marseille, France.
2
Inserm, U1068, Centre de Recherche en Cancérologie de Marseille (CRCM), Cellular Stress, Institut Paoli-Calmettes; Aix-Marseille Université UM 105; CNRS UMR 7258, Parc Scientifique et Technologique de Luminy, Marseille, France.
3
Dynabio, Luminy Biotech Entreprises, Marseille, France.
4
Inserm, U1068, Centre de Recherche en Cancérologie de Marseille (CRCM), Homologous Recombination, NHEJ and Maintenance of Genomic Integrity; Aix-Marseille Université UM 105; CNRS UMR 7258, Marseille, France.
5
Department of Pathology, Hôpital Nord / Aix-Marseille Université, Marseille, France.
6
INSERM UMR1186, Laboratory «Integrative Tumor Immunology and Genetic Oncology»; INSERM, Gustave Roussy, Université Paris-Sud, Université Paris-Saclay Villejuif, Villejuif, France.
7
Gastrointestinal & Pancreatic Oncology Group, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)/Hospital Clínic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.
8
Biomedical Department of Internal Medicine and Specialties (DiBiMIS), University of Palermo, Institute of Biomedicine and Molecular Immunology "Alberto Monroy", National Research Council (CNR), Palermo, Italy.
9
Immunomonitoring Platform Aix-Marseille Université, Marseille, France.
10
Immunomonitoring Platform Institut Paoli-Calmettes, 232 Bd Sainte Marguerite, Marseille, France.

Abstract

Vγ9Vδ2 T cells are anti-tumor immune effectors of growing interest in cancer including Pancreatic Ductal Adenocarcinoma (PDAC), an especially aggressive cancer characterized by a hypoxic and nutrient-starved immunosuppressive microenvironment. Since Butyrophilin 3 A (BTN3A) isoforms are critical activating molecules of Vγ9Vδ2 T cells, we set out to study BTN3A expression under both basal and stress conditions in PDAC primary tumors, and in novel patient-derived xenograft and PDAC-derived cell lines. BTN3A2 was shown to be the most abundant isoform in PDAC and was stress-regulated. Vγ9Vδ2 T cells cytolytic functions against PDAC required BTN3A and this activity was strongly enhanced by the agonist anti-BTN3A 20.1 mAb even under conditions of hypoxia. In PDAC primary tumors, we established that BTN3A expression and high plasma levels of soluble BTN3A were strongly associated with a decreased survival. These findings may have important implications in the design of new immunotherapeutic strategies that target BTN3A for treating PDAC.

KEYWORDS:

BTN3A; Butyrophilin 3 A; CD277; Immunotherapy; Pancreatic Ductal Adenocarcinoma

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