التفاصيل البيبلوغرافية
| العنوان: |
BTN2A1, an immune checkpoint targeting Vγ9Vδ2 T cell cytotoxicity against malignant cells. |
| المؤلفون: |
Cano, Carla E., Pasero, Christine, De Gassart, Aude, Kerneur, Clement, Gabriac, Mélanie, Fullana, Marie, Granarolo, Emilie, Hoet, René, Scotet, Emmanuel, Rafia, Chirine, Hermman, Thomas, Imbert, Caroline, Gorvel, Laurent, Vey, Norbert, Briantais, Antoine, le Floch, Anne Charlotte, Olive, Daniel |
| المصدر: |
Cell Reports; Jul2021, Vol. 36 Issue 2, pN.PAG-N.PAG, 1p |
| مستخلص: |
The anti-tumor response of Vγ9Vδ2 T cells requires the sensing of accumulated phosphoantigens (pAgs) bound intracellularly to butyrophilin 3A1 (BTN3A1). In this study, we show that butyrophilin 2A1 (BTN2A1) is required for BTN3A-mediated Vγ9Vδ2 T cell cytotoxicity against cancer cells, and that expression of the BTN2A1/BTN3A1 complex is sufficient to trigger Vγ9Vδ2 TCR activation. Also, BTN2A1 interacts with all isoforms of BTN3A (BTN3A1, BTN3A2, BTN3A3), which appears to be a rate-limiting factor to BTN2A1 export to the plasma membrane. BTN2A1/BTN3A1 interaction is enhanced by pAgs and, strikingly, B30.2 domains of both proteins are required for pAg responsiveness. BTN2A1 expression in cancer cells correlates with bisphosphonate-induced Vγ9Vδ2 T cell cytotoxicity. Vγ9Vδ2 T cell killing of cancer cells is modulated by anti-BTN2A1 monoclonal antibodies (mAbs), whose action relies on the inhibition of BTN2A1 binding to the Vγ9Vδ2TCR. This demonstrates the potential of BTN2A1 as a therapeutic target and adds to the emerging butyrophilin-family cooperation pathway in γδ T cell activation. [Display omitted] • BTN2A1 expression in cancer cells correlates with Vγ9Vδ2 T cell cytotoxicity • BTN2A1 interacts with BTN3A1/3A2/3A3, leading to enhanced plasma membrane export • B30.2 domains of both BTN3A1 and BTN2A1 are required for pAg responsiveness • Anti-BTN2A1 mAbs blocking Vγ9Vδ2TCR binding antagonize Vγ9Vδ2 T cell cytotoxicity Cano et al. show that targeting BTN2A1 with mAbs allows modulation of Vγ9Vδ2 T cell cytotoxicity against primary cancer cells. BTN2A1 expression correlates with antitumoral Vγ9Vδ2 T cell responses. BTN2A1 export at the plasma membrane is strongly enhanced by interaction with BTN3A1, and this interaction is enhanced by amino-biphosphonate treatment. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
