Suppression of macrophage function in AK-5 tumor transplanted animals: role of TGF-beta1

Transforming growth factor-beta 1 (TGF-beta1), a multifunctional cytokine secreted by various cell types has been implicated in diverse physiologic and pathophysiologic functions, including immunological, inflammatory, and neoplastic processes. AK-5 tumor cells when injected intraperitoneally grow as ascites, causing 100% mortality. Peritoneal macrophages cocultured with AK-5 cells, in vitro showed specific suppression of tumoricidal function. We report that AK-5 cells secrete the latent form of TGF-beta1, which is converted to its active homodimeric form, causing suppression of the secretion of cytocidal molecule by macrophages thereby inhibiting their cytotoxic capabilities. When macrophages are cocultured with AK-5 cells in the presence of antibodies against TGF-beta1 or the receptor II for TGF-beta, there is significant recovery in the secretion of nitric oxide and macrophage cytotoxic potential. These results suggest a major role for TGF-beta produced by the tumor cells, in the immune escape mechanisms adopted by the AK-5 tumor cells.