As noted in the goals and objectives stated for this project, it aims to create new models that test distinct hypotheses and provide new understandings for development of novel strategies in the treatment of lymphoma, myeloma, leukemia, breast cancer and renal cancer by hematopoietic stem cell transplantation. Hematopoietic stem cell transplant treatment of these diseases generally results in lymphopenia and immune compromise. The observation that in humans there is the ability to upregulate thymus function in the setting of cancer therapy-associated lymphopenia has been translated to murine models. We have initiated four parallel efforts to identify points of control in thymus function. In experiments utilizing KGF, which was found to upregulate thymus activity, we observed that while thymocyte precursor pool size and molecules involved in migration are not affected, the critical control point at the level of thymus epithelial cells are affected such that this cell population increases proliferation and total number thereby increasing niches for thymocyte maturation and overall thymopoiesis. We have initiated a new transplant model over the last year in order to better understand the mechanism by which T cells mediate anti-tumor effects in the setting of allogeneic hematopietic stem cell transplantation. The model involves transplant and then the placement subcutaneously of small numbers of malignant cells which grow locally, and are inhibited in their growth by T cell as the animal proceeds through transplant. Biopsies are taken periodically and the tissue diassociated for multi-parameter flow analysis. At this point all cell lines, models, techniques and reagents are in place and experiments have begun.Relevant cancer sites: Non-Hodgkins Lymphoma, Leukemia. Relevant Research Areas: Immunology, Bone Marrow Transplantation, Hematology/Lymph, Stem Cell Research, Regenerative Medicine, Transplantation, Biological Response Modifiers.
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