Abstract
Abstract : As antigen presenting cells capable of inducing strong cytotoxic T lymphocyte (CTL) responses to specific antigens, dendritic cells (DCs) have become prime candidates for use in cancer immunotherapy. it has been shown that treatment of DCs with tumor cell supernatants results in reduced expression of MHC class II and reduced ability to induce a CTL. response. These findings have led to the suggestion that tumors secrete soluble factors that inhibit the antigen presenting functions of DCs. in the clinical setting, immunization with DCs is well tolerated, but is unable to produce significant clinical responses. Taken together, these findings suggest that the tumors secrete immunosuppressive factors that interfere with the efficacy of DC immunotherapy. One such factor is transforming growth factor-B (TGF-B). TGF-B is a known suppressor of T cell function and recently has been implicated in decreasing the function of antigen presenting cells. Breast cancer cells secrete TGF-B and are less sensitive to TGF-B mediated growth arrest. Furthermore in breast cancer patients TGF-B immunostaining has been correlated with tumor progression. These findings suggest an important role for tumor<-derived TGF-B in the progression of mammary tumors in animals and humans. The hypothesis to he tested is that tumor%derived TGF-B mitigates the efficacy of DC vaccines. The objective is to improve the efficacy of DC based vaccines by decreasing the suppressive effects TGF-B has on DCs. The specific aims are to assess 1) the effect of TGF-B on the antigen processing and presenting functions of DCs, and 2) the effect of tumor derived TGF-B on the efficacy of DC vaccines.
Published Version
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