Cancer is the second leading cause of death in the U.S. and increases exponentially with age. Cancer immunotherapy has evolved from basic research concepts to approved treatment for selected types of tumor. One of the main goals of immunotherapy of cancer is to generate specific cytotoxic T-cells (CTL). Generation of CTL is a complex process that requires significant interactions among several players of the immune system, particularly antigen presenting cells (APC) and T cells. The biological and clinical changes associated with aging may exert a major influence in the development of an effective immune response. Indeed, there is extensive evidence that aged individuals experience either a quantitative or qualitative decline in the immune response. So, it is possible that aging by itself may affect the outcome of the immune response in patients with cancer. The decline in the immune response in the elderly has largely been attributed to impairment of T cell function. APC are central to the immune response and currently they are the most common target of active immunotherapy in cancer. Despite advances in the biology of APC, the effects of aging on dendritic cell (DC) functions in healthy individuals are relatively under-explored. This lack of knowledge is more dramatic in the setting of a tumor bearing-host. Preliminary data from our laboratory suggest that DC obtained from old mice are less efficient at inducing T-cell proliferation than DC obtained from their younger counterpart. Thus, we hypothesized that DC form aged animals have a different pattern of gene expression that may accounts for the differences observed. Therefore, to address the question of the interactions among aging, DC, and cancer we propose the following aims: I- Investigate the effects of aging in global gene expression of DC obtained from both healthy and tumor bearing hosts; II- Investigate the effects of aging on in vivo trafficking pattern of DC obtained from both healthy and tumor bearing hosts.
