A number of approaches to cancer treatment have been developed that have variable efficacy depending upon the type and stage of the tumor. Although chemotherapeutic regimens are effective for some types of cancers, immunotherapy is the most effective treatment for renal carcinoma. Thus, to further explore the utility of immunotherapy, we have focussed our research efforts on the identification of the effects and the mechanisms of action of cytokine therapy on T-cell function and on the generation of T-cell-dependent antitumor responses. In this context, we have centered our attention on interleukin-7 (IL-7). Our current research has demonstrated that T cells from IL-7-treated mice produce 3- to 9-fold more IL-4, IFN-gamma, and GM-CSF when subsequently stimulated ex vivo. Moreover, addition of IL-12 during this subsequent ex vivo stimulation can shift the cytokine response toward a type 1 pattern as demonstrated by its ability to further enhance IFN-gamma production by 70% and decrease IL-4 production by 40%. Thus, IL-7 administration """"""""primes"""""""" T cells in vivo enabling them to respond in an accelerated and enhanced fashion and this response can be manipulated by the addition of other cytokines. These studies establish IL-7 as a potent enhancer of T-cell function in vivo and support the hypothesis that IL-7 may be useful as an adjuvant for T-cell-medicated antitumor vaccine therapy. Therefore, studies are in progress to determine the ability of IL-7 to enhance responses to specific tumor antigen in vivo, and if successful, elucidate the mechanism of action. A potential concern in the use of immunotherapy for cancer treatment is that immune system alterations can occur in tumor-bearing hosts; including reduction in T-cell func-tion. Because of the ability of IL-7 to enhance T-cell function we speculated that IL-7 might be useful in the reversal/prevention of these alterations. Using a murine renal tumor, our results demonstrate that lymph nodes from tumor-bearing mice have a 50% reduction in cellularity and T cells from these mice produce reduced amounts of IFN-gamma and GM-CSF and increased amounts of IL-4. Moreover, we found that treatment of Renca-bearing mice with IL-7 prevents/reverses the reduction in lymph node cellularity. Thus, IL-7 therapy may be useful in restoring immune function in tumor-
