Fibronectin promotes the proliferation of cytotoxic T lymphocytes generated from cancer patients

We studied whether fibronectin (FN) enhances the activity of autologous tumour-reactive cytotoxic T lymphocytes (CTLs) generated from cancer patients. The proliferation of CTLs stimulated by immobilised anti-CD3 monoclonal antibody and interleukin 2 (IL-2) was enhanced three or four times by immobilised FN. whereas soluble FN did not alter the DNA synthesis of CTLs. Moreover, the cytotoxic activity of CTLs was augmented by FN stimulation against autologous tumour cells [4 h 51Cr release assay: FN(+) 16.7 +/- 4.7% vs FN (-) 11.8 +/- 3.1%; 16 h 51Cr release assay: FN(+) 24.8 +/- 4.7% vs FN (-) 16.5 +/- 5.7%, P<0.05]. The major cell surface phenotype of CTLs with FN was CD3+, CD4+ and CD25+ in 6 weeks' culture. Cytotoxicity against autologous tumour cells was inhibited by anti-HLA class I monoclonal antibody (MAb). The autologous tumour-killing activity of CTLs was suppressed by the elimination of CD4+ cells. Moreover, the cytokine production of CTLs was augmented by FN stimulation. Especially, the production of IL-2, interferon gamma (IFN-gamma), and granulocyte macrophage colony-stimulating factor (GM-CSF) was significantly augmented by FN stimulation (P<0.05). Thus, CTLs generated by FN might have both killer and helper functions, since they could lyse autologous tumour cells and secrete various cytokines, including IL-2.