Effect of blocking different TGF-β isoforms on tumor immunity (TUM5P.937)

Abstract

Abstract TGF-β is a pleiotropic cytokine with three isoforms that have significantly different physiological functions. This cytokine has potent immunosuppressive activity and has been shown to play critical roles in tumor development. TGF-β1 is also necessary for the development of T cell subsets as well as MDSC. We have previously reported that blockade of TGF-β by a monoclonal antibody 1D11, which neutralizes all three isoforms of TGF-β, improves immunosurveillance and vaccine efficacy in mouse tumor models. However, the role of individual isoforms of TGF-β is unknown. In this study, we examined the role of different TGF-β isoforms in tumor immunity by using anti-TGF-β with unique specificities in two tumor models, a lung metastasis of the BALB/c CT26 colon carcinoma and a subcutaneous TC1 lung epithelial cell tumor in B6. In the CT26 model, significant reduction of tumor burden was seen through the dual blockade of TGF-β1 and 2, or inhibition of all three TGF-β isoforms. In the TC1 model, the mice were treated with a peptide vaccine when the tumor size reached at least 5mm in diameter with/without anti-TGF-β. Although the vaccine alone induced significant regression of tumors, both types of anti-TGF-β facilitated the vaccine efficacy. These results suggest that blockade of only TGF-β1 and 2 is sufficient to facilitate natural immunosurveillance or enhance vaccine-induced tumor immunity. Currently we are investigating the effect of TGF-β isoform blockade on T cell subsets.