Cell survival and death program modulated by LMP1: implication in antitumor immunity.
The genome of Epstein-Barr virus (EBV) encodes proteins essential for malignant transformation, for example, latent membrane protein 1(LMP1). Whereas, LMP1 up-regulates anti-apoptotic proteins to support viral replication, it also potentiates apoptosis, suggesting that a viral protein contributes to the survival of the virus, and it also elicit host defense leading to the destruction of the infected cells. The antitumor immunity is exerted by infiltrated CD8+ T cells elaborating cytotoxic effectors, like Fas ligand (FasL, CD95L or CD178). As a nuclear factor-kappaB (NF-kappaB)-dependent molecule, Fas is induced by LMP1, and LMP1 enhances Fas-mediated apoptosis, according to our finding of stimulus-dependent apoptosis regulation by LMP1. Data has shown that FasL-mediated cytotoxicity has significant therapeutic effect on EBV-associated nasopharyngeal carcinoma (NPC). Recent reports suggest that mutations affecting the Fas-mediated apoptotic pathway reduce individuals' susceptibility to cancers, but cytokine-targeting therapy which precisely regulates the Fas level on tumor cells could still contribute to enhancement of antitumor immunity in cancer patients.
Zhang
Xiang-Ning
XN
Department of Pathophysiology, Guangdong Medical College, Zhanjiang, Guangdong, 524023 P.R. China. zhangxn_2006@126.com
Huang
Pei-Chun
PC
D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology; D045744:Cell Line, Tumor; D016207:Cytokines / Q000494:pharmacology; D004198:Disease Susceptibility; D020031:Epstein-Barr Virus Infections / Q000276:immunology / Q000378:metabolism*; D053222:Fas Ligand Protein / Q000378:metabolism; D004854:Herpesvirus 4, Human; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D009303:Nasopharyngeal Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D012333:RNA, Messenger / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism
D016207:Cytokines; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D053222:Fas Ligand Protein; D016328:NF-kappa B; D012333:RNA, Messenger; D014763:Viral Matrix Proteins; D019014:fas Receptor