Constitutive secretion of bioactive transforming growth factor beta 1 by small cell lung cancer cell lines

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 line, NCI-N417. Of several cytokines tested, only transforming growth factor beta 1 (TGF beta 1) severely suppressed IL-2-dependent T-cell growth. Using a specific anti-TGF beta 1 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 TGF beta 1. Further experiments showed that TGF beta 1 was secreted by four of eight SCLC lines tested. mRNA for TGF beta 1 was expressed in NCI-N417 and in SCLC-22H. Constitutive secretion of biologically active TGF beta 1 by SCLC lines suggests that tumour-derived immunosuppression may have clinical relevance.