Tgf-β1 produced by activated CD4(+) T Cells Antagonizes T Cell Surveillance of Tumor Development.

TGFβ1 is a regulatory cytokine with a crucial function in the control of T cell tolerance to tumors. Our recent study revealed that T cell-produced TGFβ1 is essential for inhibiting cytotoxic T cell responses to tumors. However, the exact TGFβ1-producing T cell subset required for tumor immune evasion remains unknown.

T cell- but not tumor cell-produced TGF-β1 promotes the development of spontaneous mammary cancer.

During their development, tumors acquire multiple capabilities that enable them to proliferate, disseminate and evade immunosurveillance. A putative mechanism is through the production of the cytokine TGF-β1. We showed in our recent studies that T cell-produced TGF-β1 inhibits antitumor T cell responses to foster tumor growth raising the question of the precise function of TGF-β1 produced by tumor cells in tumor development.

T cell surveillance of oncogene-induced prostate cancer is impeded by T cell-derived TGF-β1 cytokine.

Tolerance induction in T cells takes place in most tumors and is thought to account for tumor evasion from immune eradication. Production of the cytokine TGF-β is implicated in immunosuppression, but the cellular mechanism by which TGF-β induces T cell dysfunction remains unclear. With a transgenic model of prostate cancer, we showed that tumor development was not suppressed by the adaptive immune system, which was associated with heightened TGF-β signaling in T cells from the tumor-draining lymph nodes.

Autocrine transforming growth factor-β1 promotes in vivo Th17 cell differentiation.

TGF-β1 is a regulatory cytokine that has an important role in controlling T cell differentiation. T cell-produced TGF-β1 acts on T cells to promote Th17 cell differentiation and the development of experimental autoimmune encephalomyelitis (EAE). However, the exact TGF-β1-producing T cell subset required for Th17 cell generation and its cellular mechanism of action remain unknown.

Mammary tumor heterogeneity in the expansion of myeloid-derived suppressor cells.

The tumor microenvironment is heterogeneous for the expansion and infiltration by myeloid derived suppressor cells (MDSCs) which has been hypothesized to be dependent on tumor burden. We report a relationships between tumor size, MDSCs and T-cells; using four murine mammary tumors to assess tumor growth, infiltration and gene expression. Our analysis of cellular infiltration into tumors and gene expression used collagenase dissociated tumors and density gradient isolation of non-parenchymal cells (NPCs).