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Constitutive secretion of bioactive transforming growth factor β1 by small cell lung cancer cell lines
Authors:J.R. Fischer   H. Darjes   H. Lahm   M. Schindel   P. Drings  P.H. Krammer
Abstract:We investigated effects of soluble mediators secreted by small cell lung cancer (SCLC) cell lines on modulation of cytokine-induced growth of lymphocytes. We found that interleukin-2 (IL-2)-mediated T-cell growth was inhibited by a cytokine constitutively secreted by the SCLC cell Une, NCI-N417. Of several cytokines tested, only transforming growth factoir β1 (TGFβ1) severely suppressed IL-2-dependent T-cell growth. Using a specific antiTGFβ, antibody, we found that this antibody blocked the immunosuppressive activity secreted by NCI-N417. Thus, the NCI-N417-derived immunosuppressive molecule was serologically identified as TGFβ1. Further experiments showed that TGFβ1 was secreted by four of eight SCLC lines tested. mRNA for TGFβ1 was expressed in NCI-N417 and in SCLC-22H. Constitutive secretion of biologically active TGFβ1 by SCLC lines suggests that tumour-derived immunosuppression may have clinical relevance.
Keywords:TGFβ  i   SCLC   immunosuppression
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