Open AccessAdenovirus-mediated LIGHT gene modification in murine B-cell lymphoma elicits a potent antitumor effect
Author(s) -
Guili Hu,
Yang Liu,
Hong Li,
Dekuang Zhao,
Liuqing Yang,
Jian Qi Shen,
Hong Xiao,
Xuetao Cao,
Qingqing Wang
Publication year - 2010
Publication title -
cellular and molecular immunology/cellular and molecular immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.5
H-Index - 81
eISSN - 2042-0226
pISSN - 1672-7681
DOI - 10.1038/cmi.2010.15
Subject(s) - cytotoxic t cell , cancer research , chemokine , biology , tumor necrosis factor alpha , immunology , immune system , in vitro , biochemistry
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)-gamma 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-gamma (Mig) from tumor tissues. Thus, adenovirus-mediated LIGHT therapy might have potential utility for the prevention and treatment of B-cell lymphoma.