Experimental Studies
Molecular mechanism of AFP-specific liver tumor vaccines killing HepG2 hepatocellular carcinoma(HCC) cells in vitro
Liu Yang, Wang Yueru, Ding Guanghui, Yang Tingsong, Yao Le, Xun Linjuan, Zhuang Ying, Zhang Baihe, Lu Chongde
Published 2016-01-28
Cite as Chin J Hepatobiliary Surg, 2016,22(1): 52-55. DOI: 10.3760/cma.j.issn.1007-8118.2016.01.016
Abstract
ObjectiveTo prepare AFP-specific CD8+ T lymphocyte liver tumor vaccine, and investigate its anti-tumor activity in vitro and the related molecular mechanism.
MethodsWe used AFP-specific dendritic cells (DC) which were activated by either AFP peptide (AFP542-550)-pulsed or lenti-AFP-engineered to activate AFP-specific CD8+ T lymphocyte in vitro, and investigated the anti-tumor activity of AFP-specific CD8+ T lymphocytes (AFP-CD8+ -CTL). The anti-human CD134 or anti-human CD28 monoclonal antibody was used to block or activate AFP-CD8+ -CTL and FasL signaling, and cytokines released such as IL-2, IFN-γ, perforin, granzyme B and FasL were detected to determine the direct role of perforin/granzyme B pathway in this anti-tumor effect.
ResultsThe results demonstrated that anti-human CD134 monoclonal antibody could block the activity of AFP-CD8+ -CTL, which could not efficiently kill HepG2 cells by decreasing the level of IL-2, IFN-γ, perforin and granzyme B significantly (P<0.05). When AFP-CD8+ -CTL was cocultured with anti-human CD28 monoclonal antibody, the AFP-specific T cells could efficiently kill HepG2 cells by significantly increasing the level of IL-2, IFN-γ, perforin and granzyme B (P<0.05). No obvious change was observed on FasL level.
ConclusionsThe anti-human CD134 and anti-human CD28 monoclonal antibody could inhibit and activate AFP-CD8+ -CTL. The perforin/granzyme B pathway might play an important role in the anti-tumor activity of liver tumor vaccines.
Key words:
Hepatocellular carcinoma; Alpha-fetoprotein; Tumor vaccine; Molecular Mechanism
Contributor Information
Liu Yang
Hepatobiliary Surgery Division, Tenth People's Hospital, Tongji University, Shanghai 20072, China
Wang Yueru
Ding Guanghui
Yang Tingsong
Yao Le
Xun Linjuan
Zhuang Ying
Zhang Baihe
Lu Chongde