TY - JOUR
T1 - BTN3A is a prognosis marker and a promising target for Vγ9Vδ2 T cells based-immunotherapy in pancreatic ductal adenocarcinoma (PDAC)
AU - Montalto, Giuseppe
AU - Loncle, Céline
AU - Benyamine, Audrey
AU - Secq, Véronique
AU - Chrétien, Anne-Sophie
AU - Castanier, Céline
AU - Vila-Navarro, Elena
AU - Blazquez, Juan-Luis
AU - Modesti, Mauro
AU - Foucher, Etienne
AU - Gironella, Meritxell
AU - Dusetti, Nelson
AU - Dagorn, Jean-Charles
AU - Chouaib, Salem
AU - Iovanna, Juan
AU - Olive, Daniel
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
UR - http://hdl.handle.net/10447/299166
UR - http://www.tandfonline.com/loi/koni20
M3 - Article
VL - 7
SP - e1372080-
JO - OncoImmunology
JF - OncoImmunology
SN - 2162-4011
ER -