Effects of transforming growth factor beta1 expression in a rat colon carcinoma: growth inhibition, leukocyte infiltration and production of interleukin-10 and tumor necrosis factor alpha.

The cytokine transforming growth factor beta-1 (TGFbeta1), was transfected into a TGFbeta1-negative rat colon carcinoma. The growth of isografts of TGFbeta1-expressing tumors was compared to that of vector control transfectants. The TGFbeta1 transfectant grew significantly more slowly after intrahepatic isografting than did vector control and wild-type tumors. The TGFbeta1-transfected tumor tissue had significantly greater infiltration of both CD4+ and CD8+ T lymphocytes than did the vector control tumor. The tumor-infiltrating leukocytes (TIL) from TGFbeta1-transfected tumor secreted significantly more of the cytokines interleukin-10 (IL-10) and tumor necrosis factor alpha (TNFalpha) than did TIL from the vector control tumor. The TGFbeta1 transfectant also demonstrated a significantly slower outgrowth in immunodeficient SCID mice, supporting a non-T-lymphocyte-dependent mechanism for the tumor retardation. In SCID mice, the TGFbeta1-transfected tumor demonstrated significantly greater infiltration of both granulocytes and macrophages than did the vector control transfectant. We also demonstrated a direct inhibitory effect of rat TNFalpha on tumor proliferation in vitro. These results suggest that TGFbeta1 induces a local secretion of immunomodulating cytokines and that this may influence monocytes, lymphocytes and granulocytes to retard tumor outgrowth. (Less)