Date of Award
Doctor of Philosophy
Field of Study
Graduate School of Biomedical Sciences
Rance E. Berg
Tumor metastatic relapse is the major cause of cancer-associated mortality. Metastatic relapse is believed to arise from quantities of tumor cells that are below detectable thresholds, which are able to resist radio/chemotherapy by obtaining a dormant state and hiding in certain organs, i.e., tumor reservoirs. The thymus, the central T-cell immune organ, has been suggested to be a pre-metastatic tumor reservoir for B-lymphoma cells. However, it remains unknown whether the thymus is able to harbor nonlymphoid solid tumor cells, and whether chemotherapy can thoroughly eliminate cancer cells in the thymus. If chemotherapy is not able to eliminate these cells in the thymus, then what processes allow for this? Melanoma cell–inoculated and genotoxic doxorubicin-treated mouse model systems were used to determine that the thymus, particularly the atrophied thymus, was able to harbor bloodstream–circulating melanoma cells. In addition, chemotherapy-induced DNA-damage response triggered p53 activation in nonmalignant thymic cells, which in turn resulted in thymocyte death and thymic epithelial cell senescence to develop an inflammatory thymic microenvironment. This inflammatory condition induced thymic-harbored minimal tumor cells to acquire a chemo-resistant state.
"Atrophied thymus, a tumor reservoir for harboring melanoma cells" Fort Worth, Tx: University of North Texas Health Science Center;