A wealth of successful pre-clinical immunotherapy-based treatment protocols against cancer have been documented, yet only a limited number of clinical trials have proven to be successful. A common consensus among clinical and bench-side researchers is that a combination of several treatment modalities should be used to achieve complete tumor regression. In recent years, evidence that chemotherapy agents can be used to enhance immune-based therapies has emerged. The specific aims described below are designed to evaluate novel treatment modalities against cancer using chemotherapy agents that have the ability to sensitize tumors to both innate and adaptive anti-tumor immune responses. 1. Examine the effect of different chemotherapy agents in their ability to modify tumor susceptibility to autologous and allogeneic natural killer (NK) and T cell -mediated apoptosis in vitro. 2. In vivo confirmation and evaluation of selected agents in murine syngeneic and allogeneic hematopoietic stem cell transplantation (HCT) tumor models. The results of these studies will lay a foundation for NK cell-based and T cell-based therapies which could lead to more effective treatments for cancer patients. In addition to defining mechanisms how the various chemotherapy agents may influence NK or T cell anti-tumor responses, several subsidiary projects derived from this research will most likely develop.