Mammary tumor-derived. TGF-β impairs crucial innate immune responses in tumor hosts

The D1-DMBA-3 mouse mammary tumor has been shown to produce several factors that modulate the immune system. In this study we document the production of TGF-β1 not only by the tumor cells, but also by cells of the innate and adaptive immune system in tumor-bearing animals. Presence of TGF-β1 was studied in supernatants from the DA3 cell line, which was isolated from the D1-DMBA-3 tumor. The levels of this molecule were also evaluated in the sera, macrophages and T lymphocytes from tumor bearers and normal mice. The expression of this molecule was assessed by means of ELISA. Addition of exogenous TGF-β1 down regulated innate immune functions in macrophages of BALB/c mice, such as the production of the IL-12 and nitric oxide. The data presented herein demonstrate that TGF-β1 is an immunomodulating factor produced not only by the tumor cells themselves, but also by macrophages and T cells from tumor-bearing animals. These results suggest that TGF-β1 contributes to the impaired innate immune responses exhibited by mice bearing this mammary tumor.