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Dr. Sykes and her team have developed novel strategies for achieving graft-versus-tumor effects without graft-versus-host disease following hematopoietic cell transplantation (HCT). One strategy involved their observation that graft-vs-host (GVH) alloresponses can remain within the lymphohematopoietic system, where they mediate graft-vs-leukemia (GVL) responses, without accumulating in the epithelial target tissues where graft-versus-host disease (GVHD) occurs. We demonstrated a critical role of GVHD target tissue inflammation, such as that induced by toll-like receptor stimuli, in converting a beneficial "lymphohematopoietic GVH response" to GVHD. This control by inflammation is elicited at the level of access of activated GVH-reactive T cells to the GVHD target tissues. Clinical non-myeloablative HCT trials have been carried out on the basis of this approach to separating GVL from GVHD.
The Sykes lab has pioneered minimal conditioning approaches for using HCT to achieve allograft tolerance. These include monoclonal antibodies or costimulatory blockade to eliminate host resistance to engraftment of allogeneic and xenogeneic bone marrow cells, allowing creation of a mixed chimeric state, and with it the induction of specific transplantation tolerance. Studies to understand the mechanisms of peripheral tolerance of CD4 and CD8 T cells that encounter donor antigens on bone marrow cells in the presence of costimulatory blockade provided evidence that anergy precedes specific deletion of peripheral donor-reactive T cells, and this is followed by central deletional tolerance of donor-reactive T cells that develop after chimerism is established. Insights into the roles of PD-1, LAG-3, indirect presentation and various cell-cell interactions in the peripheral tolerance processes have been published by our group.
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论文共 171 篇作者统计合作学者相似作者
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bioRxiv : the preprint server for biology (2024)
Wenyu Jiao,Mercedes Martinez, Constanza Bay Muntnich,Julien Zuber,Christopher Parks,Aleksandar Obradovic,Guangyao Tian,Zicheng Wang, Katherine D. Long,Elizabeth Waffarn,Kristjana Frangaj,Rebecca Jones,
EBIOMEDICINE (2024): 105028-105028
Sarah Merl, Sarah Merl,Bryan Chen, M. Esad Gunes, Hussein Atta, Kryscilla Yang,Dilrukshi Ekanayake-Alper,Dilrukshi Ekanayake-Alper, Dominik Hajosi, Fei Huang, Brittany Bhola, Satyajit Patwardhan,
Frontiers in Transplantation (2024)
TRANSPLANTATIONno. 10 (2023): 94-94
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TRANSPLANTATIONno. 10 (2023): 95-95
HEPATOLOGY (2023): S256-S257
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Jianing Fu,Zicheng Wang,Mercedes Martinez,Aleksandar Obradovic,Wenyu Jiao,Kristjana Frangaj,Rebecca Jones,Xinzheng V. Guo,Ya Zhang, Wan- Kuo, Huaibin M. Ko,Alina Iuga,
The Journal of experimental medicineno. 1 (2023)
Lillian M. Tran,Camila Macedo,Alan F. Zahorchak,Xinyan Gu,Beth Elinoff,Aatur D. Singhi, Brian Isett,Adriana Zeevi,Megan Sykes, Kevin Breen, Avantika Srivastava, Erin M. Ables,
SCIENCE TRANSLATIONAL MEDICINEno. 717 (2023)
Cancer cellno. 7 (2023): 1207-1221.e12
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