Targeting Neovascularization in Graft-Versus-Host Disease
In many blood cancers, allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents the only treatment with the potential for cure. Graft-versus-host disease (GVHD), however afflict between 30-80% of patients receiving allo-HSCT and remains a major cause of death. The primary cause of GVHD is known to be donor's immune cells, which can recognize recipient's tissues as foreign and attack indiscriminately, often targeting both cancer cells and normal tissues. Our recent studies in mouse models have demonstrated a previously unknown association between growth of new blood vessels and development of GVHD. We found that organs involved with GVHD have evidence of new vessel growth, and that mice with GVHD have increased numbers of circulating cells called endothelial progenitor cells (EPCs), which are recruited in the formation of new vessels. Reducing numbers of EPCs by blocking anti-VE Cadherin resulted in decreased formation of new vessels as well as decreased GVHD. Importantly, the ability of donor T cells to attack cancer cells was not compromised by the antibody treatment. In this project, we will study what leads to these new blood vessels to develop. In addition, we will determine how the growth of new vessels affects growth and spread of cancer cells, and their interactions with immune cells in the context of HSCT. We hope that our approach would reveal a fresh understanding of the GVHD process. Further, we hope to understand how new blood vessel formations in the recipients of HSCT affect the development and spread of cancerous cells.