Multifaceted inhibition of anti-tumour immune mechanisms by soluble tumour necrosis factor receptor type I.
Soluble tumour necrosis factor receptor type I (sTNFRI) is a potent inhibitor of TNF with the potential to suppress a variety of effector mechanisms important in tumour immunity. That sTNFRI influences tumour survival in vivo is suggested by results from human clinical trials of Ultrapheresis, an experimental extracorporeal treatment for cancer. While the considerable clinical benefit provided by Ultrapheresis is correlated with the removal of plasma sTNFRI, there is no direct evidence that sTNFRI inhibits immune mechanisms which mediate tumour cell elimination. To evaluate formally the ability of sTNFRI to inhibit these mechanisms, we have engineered sTNFRI production into the TNF-sensitive murine fibrosarcoma cell line, L929. Soluble TNFRI-secreting L929 cells display increased resistance to direct lysis by TNF, and to lysis by syngeneic lymphokine-activated killer cells and cytotoxic T cells. These findings confirm the suggestion that sTNFRI inhibits immunological mechanisms important in tumour cell eradication, and further support a role for sTNFRI in tumour survival in vivo. In addition, these observations suggest the development of methods for more specific removal and/or inactivation of sTNFRI as promising new avenues for cancer immunotherapy.
Department of Microbiology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins 80523, USA.
C L
CL
Selinsky
K L
KL
Boroughs
W A
WA
Halsey
M D
MD
Howell
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D005354:Fibrosarcoma / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis / Q000276:immunology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D011994:Recombinant Proteins / Q000276:immunology; D012995:Solubility; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha