BEGIN:VCALENDAR
VERSION:2.0
PRODID:-//Talks.cam//talks.cam.ac.uk//
X-WR-CALNAME:Talks.cam
BEGIN:VEVENT
SUMMARY:Targeting GARP on human Tregs:  a novel approach for the immunothe
 rapy of cancer? - Prof. Sophie Lucas\; The de Duve Institute\, Brussels
DTSTART:20191113T120000Z
DTEND:20191113T130000Z
UID:TALK127420@talks.cam.ac.uk
CONTACT:Bobbie Claxton
DESCRIPTION:Transforming growth factor-1 (TGF-1) is one of very few 
 cytokines produced in a latent form\, requiring activation to exert any of
  its vastly diverse effects on development\, immunity\, or cancer. Regulat
 ory T cells (Tregs) suppress immune cells within close proximity by activa
 ting latent TGF-1 presented by GARP to integrin αVβ8 on their surface
 . We solved the crystal structure of GARP:latent TGF-1 bound to an anti
 body that stabilizes the complex and blocks release of active TGF-1. Th
 is reveals how GARP exploits an unusual medley of interactions\, including
  fold complementation by the N-terminus of TGF-1\, to chaperone and ori
 ent the cytokine for binding and activation by αVβ8. Our work further el
 ucidates the mechanism of antibody-mediated blockade of TGF-1 activatio
 n and immunosuppression by Tregs. We also explored the therapeutic potenti
 al of blocking anti-GARP:TGF-1 antibodies in murine models of cancer. F
 inally\, we present analyses of GARP-expressing Tregs in human melanoma sa
 mples\, which suggest that targeting GARP on human Tregs with blocking ant
 ibodies could represent an novel approach for the immunotherapy of cancer.
 \n\n\nSelected publications\n\n1.	Liénart S.\, Merceron R.\, Vanderaa C.\
 , Lambert F.\, Colau D.\, Stockis J.\, van der Woning B.\, De Haard H.\, S
 aunders M.\, Coulie P.G.\, Savvides S.N.\, Lucas S. Structural basis of la
 tent TGF-β1 presentation and activation by GARP on human regulatory T cel
 ls.\nScience. 362(6417):952-956\, 2018 \n						\n2.	Stockis J.\, Liénart 
 S.\, Colau D.\, Collignon A.\, Nishimura S.L.\, Sheppard D.4\, Coulie P.G.
 \, Lucas S. Blocking immunosuppression by human Tregs in vivo with antibod
 ies targeting integrin αVβ8.\nProc Natl Acad Sci U S A. 114(47):E10161-E
 10168\, 2017.	\n					\n3.	Cuende J.\, Liénart S.\, Dedobbeleer O.\, van d
 er Woning B.\, De Boeck G.\, Stockis1 J.\, Huygens C.\, Colau D.\, Somja J
 .\, Delvenne P.\, Hannon M.\, Baron F.\, Dumoutier L.\, Renauld J.-C.\, De
  Haard H.\, Saunders M.\, Coulie P.G. and Lucas S. Monoclonal antibodies a
 gainst GARP/TGF-β1 complexes inhibit the immunosuppressive activity of hu
 man regulatory T cells in vivo.\nScience Translational Medicine. 7(284): 2
 84ra56\, 2015. \n
LOCATION:Babraham - The Cambridge Building - Petersfield Lecture Theatre
END:VEVENT
END:VCALENDAR