Differential expression of transforming growth factor beta 1 and interleukin 10 in progressing and regressing areas of primary melanoma

The coexistence of tumor specific immunity with a progressing tumor remains a major paradox of tumor immunology. This enigma is most evident in partia lly regressing melanomas, where efficient eradication of tumor cells is clo sely linked to uncontrolled tumor growth. Mechanisms involved in this diffe rential susceptibility of tumor cells to the host immune response may inclu de altered production of immunosuppressive cytokines, i.e., transforming gr owth factor (TGF) beta or interleukin (IL) 10. Since only limited amounts o f tissue samples are available from primary tumors, a semi-quantitative rev erse transcriptase polymerase chain reaction (RT-PCR) was established which allowed to estimate the amount of cytokine mRNA expressed in a small numbe r of melanoma cells segregated by indirect immunomagnetic isolation. Thereb y, we determined the expression of TGF-beta 1 and IL-10 mRNA in melanoma ce lls obtained from regressing and progressing areas of 9 primary tumors. TGF -beta 1 mRNA could be detected in all undiluted samples from progressing ar eas and in 7 samples from regression zones. Titration of the sample reveale d that in 6 cases TGF-beta 1 mRNA could be detected at a significant higher titer in progressing than in regressing areas. IL-10 mRNA was present in 8 samples obtained from progressing and in 7 samples from regressing tumor a reas. In 6 tumors IL-10 mRNA was detectable at a higher titer in the progre ssion zones. Specificity of the PCR amplification was confirmed with a seri es of restriction enzyme digestions of the resulting PCR product. Based on these findings the hypothesis that immunosuppressive cytokines, such as TGF -beta 1 or IL-10, represent important factors for the melanoma cells to esc ape immune surveillance is supported.