Soluble tumor necrosis factor receptor type I enhances tumor development and persistence in vivo

Secretion of human soluble tumor necrosis factor receptor type I (sTNFRI) b y the mouse fibrosarcoma cell line, L929, previously has been demonstrated to confer resistance to in vitro lysis by TNF and to LAK- and CTL-mediated cytolysis, These findings suggest that, in vivo sTNFRI contributes to tumor survival by inhibiting these immunologic mechanisms. To evaluate this hypo thesis, we compared the growth of sTNFRI-secreting L929 cells with that of the unmodified parental fibrosarcoma in an in vivo mouse transplantation mo del. Secretion of sTNFRI by L929 cells markedly enhanced their tumorigenici ty and persistence in syngeneic recipients. This benefit was abrogated by s TNFRI-neutralizing antibodies induced by immunization prior to tumor challe nge. These data demonstrate that sTNFRI directly influences tumor formation and persistence in vivo and suggest the selective removal and/or inactivat ion of sTNFRI as a promising new avenue for cancer immunotherapy. (C) 2000 Academic Press.