INTERFERON INDUCIBLE TRANSCRIPTION FACTORS: ROLES IN OCU

National Eye Institute

Investigators

Linked publications & trials

Abstract

Interferon gamma (IFNg) plays important roles in the regulation of systemic immunity and host mechanisms of tumor surveillance. It is efficacious in treatment of certain neoplastic diseases and its anti-tumor effects is thought to derive from activation of immunological effector cells. Furthermore, INFg-inducible factors (IRF-1 and ICSBP) that are thought to be tumor suppressors are deleted in a number of myelogenic leukemias. In this study, we examined whether IFNg can act directly on tumor cells in vivo to suppress their growth. We generated double transgenic (DT) mice with targeted expression of IFNg and the oncogenic SV40 T-Antigen (TAg) in the lens. The DT mice developed lens tumors in utero. In contrast to the TAg mice, the tumor burden progressively decreased with age, resulting in complete regression of the tumor in adult DT mice. Splenic and lymph node T cells from TAg or DT mice did not proliferate in response to TAg, indicating that both strains are tolerant to the transgene. We also found significant increase in the expression of IRF-1, ICSBP and the pro-apoptotic protein, caspase-1 (ICE). Taken together, our data suggest that tumor regression in these eyes resulted from direct anti-tumor effects of IFNg and that the primary impact of IFNg is on tumor progression and not on tumor initiation. On going studies seek to characterize the underlying mechanism. Particular focus is on the role of pro-apoptotic pathways in elimination of neoplastic lens cells.