Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC010957-04
Application #
8349246
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2011
Total Cost
$1,166,782
Indirect Cost

  Institution

Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Kim, Hye Kyung; Waickman, Adam T; Castro, Ehydel et al. (2016) Distinct IL-7 signaling in recent thymic emigrants versus mature naïve T cells controls T-cell homeostasis. Eur J Immunol 46:1669-80
Williams, Joy A; Zhang, Jingjing; Jeon, Hyein et al. (2014) Thymic medullary epithelium and thymocyte self-tolerance require cooperation between CD28-CD80/86 and CD40-CD40L costimulatory pathways. J Immunol 192:630-40
Bodogai, Monica; Lee Chang, Catalina; Wejksza, Katarzyna et al. (2013) Anti-CD20 antibody promotes cancer escape via enrichment of tumor-evoked regulatory B cells expressing low levels of CD20 and CD137L. Cancer Res 73:2127-38
Farthing, Don E; Buxbaum, Nataliya P; Bare, Catherine V et al. (2013) Sensitive GC-MS/MS method to measure deuterium labeled deoxyadenosine in DNA from limited mouse cell populations. Anal Chem 85:4613-20
Gress, Ronald E; Miller, Jeffrey S; Battiwalla, Minoo et al. (2013) Proceedings from the National Cancer Institute's Second International Workshop on the Biology, Prevention, and Treatment of Relapse after Hematopoietic Stem Cell Transplantation: Part I. Biology of relapse after transplantation. Biol Blood Marrow Transplant 19:1537-45
Carpenter, Robert O; Evbuomwan, Moses O; Pittaluga, Stefania et al. (2013) B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma. Clin Cancer Res 19:2048-60
Kim, Grace Y; Ligons, Davinna L; Hong, Changwan et al. (2012) An in vivo IL-7 requirement for peripheral Foxp3+ regulatory T cell homeostasis. J Immunol 188:5859-66
El-Kassar, Nahed; Flomerfelt, Francis A; Choudhury, Baishakhi et al. (2012) High levels of IL-7 cause dysregulation of thymocyte development. Int Immunol 24:661-71
Olkhanud, Purevdorj B; Damdinsuren, Bazarragchaa; Bodogai, Monica et al. (2011) Tumor-evoked regulatory B cells promote breast cancer metastasis by converting resting CD4? T cells to T-regulatory cells. Cancer Res 71:3505-15
Mackall, Crystal L; Fry, Terry J; Gress, Ronald E (2011) Harnessing the biology of IL-7 for therapeutic application. Nat Rev Immunol 11:330-42

Showing the most recent 10 out of 23 publications