Adenovirus-mediated LIGHT gene modification in murine B-cell lymphoma elicits a potent antitumor effect

摘要

Here,we investigated the antitumor effect of adenovirus-mediated gene transfer of LIGHT,the tumor-necrosis factor(TNF)superfamily member also known as TNFSF14,in the murine A20 B-cell lymphoma.LIGHT gene modification resulted in upregulated expression of Fas and the accessory molecule-intercellular adhesion molecule-1(ICAM-1)on A20 cells and led to enhanced A20 cell apoptosis.LIGHT-modified A20 cells effectively stimulated the proliferation of T lymphocytes and interferon(IFN)-c production in vitro.Immunization of BALB/c mice with a LIGHT-modified A20 cell vaccine efficiently elicited protective immunity against challenge with the parental tumor cell line.Adenovirus-mediated gene transfer of LIGHT by intratumoral injection exerted a very potent antitumor effect against pre-existing A20 cell lymphoma in BALB/c mice.This adenovirus-mediated LIGHT therapy induced substantial splenic natural killer(NK)and cytotoxic T lymphocyte(CTL)activity,enhanced tumor infiltration by inflammatory cells and increased chemokine expression of CC chemokine ligand 21(CCL21),IFN-inducible protein-10(IP-10)and monokine induced by IFN-c(Mig)from tumor tissues.Thus,adenovirus-mediated LIGHT therapy might have potential utility for the prevention and treatment of B-cell lymphoma.