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Transcript of Cytomegalovirus promotes expansion of pre- existing T-cell immunity following allogeneic...
![Page 1: Cytomegalovirus promotes expansion of pre- existing T-cell immunity following allogeneic transplantation significantly modulating chimerism status Rob.](https://reader035.fdocuments.in/reader035/viewer/2022062806/5697c02c1a28abf838cd951b/html5/thumbnails/1.jpg)
Cytomegalovirus promotes expansion of pre-existing T-cell immunity following allogeneic transplantation significantly modulating chimerism status
Rob S. Sellar, Frederick Arce Vargas, Jake Y. Henry, Stephanie Verfuerth, Sarah Charrot, Sergio A. Quezada, Stephen Mackinnon, Kirsty J. Thomson,
and Karl S. Peggs*
University College London Cancer Institute
![Page 2: Cytomegalovirus promotes expansion of pre- existing T-cell immunity following allogeneic transplantation significantly modulating chimerism status Rob.](https://reader035.fdocuments.in/reader035/viewer/2022062806/5697c02c1a28abf838cd951b/html5/thumbnails/2.jpg)
The Dogma
• CMV reactivations are increased if you T-deplete• Highest risk population R+/D-• New therapeutic strategies are needed
![Page 3: Cytomegalovirus promotes expansion of pre- existing T-cell immunity following allogeneic transplantation significantly modulating chimerism status Rob.](https://reader035.fdocuments.in/reader035/viewer/2022062806/5697c02c1a28abf838cd951b/html5/thumbnails/3.jpg)
What if it is wrong?
![Page 4: Cytomegalovirus promotes expansion of pre- existing T-cell immunity following allogeneic transplantation significantly modulating chimerism status Rob.](https://reader035.fdocuments.in/reader035/viewer/2022062806/5697c02c1a28abf838cd951b/html5/thumbnails/4.jpg)
What if it is wrong?
CMV reactivations
![Page 5: Cytomegalovirus promotes expansion of pre- existing T-cell immunity following allogeneic transplantation significantly modulating chimerism status Rob.](https://reader035.fdocuments.in/reader035/viewer/2022062806/5697c02c1a28abf838cd951b/html5/thumbnails/5.jpg)
What if it is wrong?
CMV reactivations Days of treatment
![Page 6: Cytomegalovirus promotes expansion of pre- existing T-cell immunity following allogeneic transplantation significantly modulating chimerism status Rob.](https://reader035.fdocuments.in/reader035/viewer/2022062806/5697c02c1a28abf838cd951b/html5/thumbnails/6.jpg)
Problematic CMV reactivations are associated with low levels of recipient chimerism
CMV reactivations
![Page 7: Cytomegalovirus promotes expansion of pre- existing T-cell immunity following allogeneic transplantation significantly modulating chimerism status Rob.](https://reader035.fdocuments.in/reader035/viewer/2022062806/5697c02c1a28abf838cd951b/html5/thumbnails/7.jpg)
Problematic CMV reactivations are associated with low levels of recipient chimerism
CMV reactivations Days of treatment
![Page 8: Cytomegalovirus promotes expansion of pre- existing T-cell immunity following allogeneic transplantation significantly modulating chimerism status Rob.](https://reader035.fdocuments.in/reader035/viewer/2022062806/5697c02c1a28abf838cd951b/html5/thumbnails/8.jpg)
Problematic CMV reactivations are restricted to patients with significant GvHD
CMV reactivations
![Page 9: Cytomegalovirus promotes expansion of pre- existing T-cell immunity following allogeneic transplantation significantly modulating chimerism status Rob.](https://reader035.fdocuments.in/reader035/viewer/2022062806/5697c02c1a28abf838cd951b/html5/thumbnails/9.jpg)
Problematic CMV reactivations are restricted to patients with significant GvHD
CMV reactivations Days of treatment
![Page 10: Cytomegalovirus promotes expansion of pre- existing T-cell immunity following allogeneic transplantation significantly modulating chimerism status Rob.](https://reader035.fdocuments.in/reader035/viewer/2022062806/5697c02c1a28abf838cd951b/html5/thumbnails/10.jpg)
Patients with significant GvHD had lower absolute lymphocyte counts
![Page 11: Cytomegalovirus promotes expansion of pre- existing T-cell immunity following allogeneic transplantation significantly modulating chimerism status Rob.](https://reader035.fdocuments.in/reader035/viewer/2022062806/5697c02c1a28abf838cd951b/html5/thumbnails/11.jpg)
CMV appears to influence levels of recipient chimerism
![Page 12: Cytomegalovirus promotes expansion of pre- existing T-cell immunity following allogeneic transplantation significantly modulating chimerism status Rob.](https://reader035.fdocuments.in/reader035/viewer/2022062806/5697c02c1a28abf838cd951b/html5/thumbnails/12.jpg)
CMV appears to influence levels of recipient chimerism
![Page 13: Cytomegalovirus promotes expansion of pre- existing T-cell immunity following allogeneic transplantation significantly modulating chimerism status Rob.](https://reader035.fdocuments.in/reader035/viewer/2022062806/5697c02c1a28abf838cd951b/html5/thumbnails/13.jpg)
CMV appears to influence levels of recipient chimerism
![Page 14: Cytomegalovirus promotes expansion of pre- existing T-cell immunity following allogeneic transplantation significantly modulating chimerism status Rob.](https://reader035.fdocuments.in/reader035/viewer/2022062806/5697c02c1a28abf838cd951b/html5/thumbnails/14.jpg)
CMV influences chimerism even in the absence of GvHD
![Page 15: Cytomegalovirus promotes expansion of pre- existing T-cell immunity following allogeneic transplantation significantly modulating chimerism status Rob.](https://reader035.fdocuments.in/reader035/viewer/2022062806/5697c02c1a28abf838cd951b/html5/thumbnails/15.jpg)
Streptamer positive cells are exclusively of recipient origin
![Page 16: Cytomegalovirus promotes expansion of pre- existing T-cell immunity following allogeneic transplantation significantly modulating chimerism status Rob.](https://reader035.fdocuments.in/reader035/viewer/2022062806/5697c02c1a28abf838cd951b/html5/thumbnails/16.jpg)
Streptamer positive cells are exclusively of recipient origin
Donor
Recipient
CD4+
CD8+ Strep-
CD8+ Strep+
Patient 1 Patient 2 Patient 3
![Page 17: Cytomegalovirus promotes expansion of pre- existing T-cell immunity following allogeneic transplantation significantly modulating chimerism status Rob.](https://reader035.fdocuments.in/reader035/viewer/2022062806/5697c02c1a28abf838cd951b/html5/thumbnails/17.jpg)
DLI can be followed by a primary immune response to CMV
Donor
Recipient
Pre-DLI
4 weeks
8 weeks
12 weeks
18 weeks
CD8+ Strep- CD8+ Strep+ CD4+
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Conclusions
• recipient-derived virus-specific T cells that have escaped deletion during non-myeloablative conditioning can protect against recurrent CMV infection
• expansion of these cells post transplant has a significant influence on levels of recipient chimerism
• “Campath Paradox” - T cell-depletion in the R+D- setting may paradoxically foster more rapid reconstitution of protective antiviral immunity by reducing graft-versus-host directed alloreactivity and the associated elimination of the recipient T cell compartment
![Page 19: Cytomegalovirus promotes expansion of pre- existing T-cell immunity following allogeneic transplantation significantly modulating chimerism status Rob.](https://reader035.fdocuments.in/reader035/viewer/2022062806/5697c02c1a28abf838cd951b/html5/thumbnails/19.jpg)
Acknowledgements
• UCL Cancer Institute• Tumour Immunogy Group– Dr Karl S Peggs
– Dr Sergio A Quesada
– Dr Frederick Arce Vargas
– Jake Y Henry
• Royal Free Hospital – Professor Stephen Mackinnon
– Stephanie Verfuerth
• UCLH – Dr Kirsty Thomson
– Dr Sarah Charrot