EBV-Associated Lymphoproliferative Disorders: Classification and Treatment

Carbone, Antonino; Gloghini, Annunziata; Dotti, Giampietro

doi:10.1634/theoncologist.2008-0036

Cited by 236 publications

(190 citation statements)

References 71 publications

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“…EBV is the causal agent of infectious mononucleosis (IM), a common benign disorder, and is associated with several human malignancies [22][23]. Worldwide, more than 95% of adults are infected with EBV [24], with the majority of infections occurring during childhood when they produce minimal symptoms.…”

Section: Ebv Life Cyclementioning

confidence: 99%

Immunotherapy against cancer-related viruses

2016

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Approximately 12% of all cancers worldwide are associated with viral infections. To date, eight viruses have been shown to contribute to the development of human cancers, including Epstein-Barr virus (EBV), Hepatitis B and C viruses, and Human papilloma virus, among others. These DNA and RNA viruses produce oncogenic effects through distinct mechanisms. First, viruses may induce sustained disorders of host cell growth and survival through the genes they express, or may induce DNA damage response in host cells, which in turn increases host genome instability. Second, they may induce chronic inflammation and secondary tissue damage favoring the development of oncogenic processes in host cells. Viruses like HIV can create a more permissive environment for cancer development through immune inhibition, but we will focus on the previous two mechanisms in this review. Unlike traditional cancer therapies that cannot distinguish infected cells from non-infected cells, immunotherapies are uniquely equipped to target virus-associated malignancies. The targeting and functioning mechanisms associated with the immune response can be exploited to prevent viral infections by vaccination, and can also be used to treat infection before cancer establishment. Successes in using the immune system to eradicate established malignancy by selective recognition of virus-associated tumor cells are currently being reported. For example, numerous clinical trials of adoptive transfer of ex vivo generated virus-specific T cells have shown benefit even for established tumors in patients with EBV-associated malignancies. Additional studies in other virus-associated tumors have also been initiated and in this review we describe the current status of immunotherapy for virus-associated malignancies and discuss future prospects.

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Section: Ebv Life Cyclementioning

confidence: 99%

Immunotherapy against cancer-related viruses

2016

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“…Necropsies were performed at each facility after death (case Nos. [2][3][4][5] 16 but additional analysis was performed in the present study.…”

Section: Animalsmentioning

confidence: 99%

“…Besides in situ hybridization for EBER, immunohistochemistry is used to detect EBV-related antigens, including EBV-encoded nuclear antigen 2 (EBNA2) and latent membrane protein 1 (LMP1). 5 Although a previous study suggested that an LMP1 antibody did not cross-react with macaque LCV antigen, 28 cells reacting with an EBNA2 antibody have been detected in sections of lymphomas in rhesus and cynomolgus macaques (Macaca fascicularis). 2,4,10,20,24,28 Therefore, immunostaining for EBNA2 is a possible option for detecting LCV in Japanese macaques.…”

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confidence: 94%

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Characterization of Spontaneous Malignant Lymphomas in Japanese Macaques (Macaca fuscata)

et al. 2014

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Lymphomas are common spontaneous tumors in nonhuman primates but remain poorly characterized in Japanese macaques (Macaca fuscata). This study examined 5 cases of spontaneous malignant lymphoma in Japanese macaques, focusing on the immunophenotypes and presence of simian lymphocryptoviruses, which are Epstein-Barr virus-related herpesviruses in nonhuman primates. The macaques with lymphoma were 5 to 28 years old, indicating that lymphomas develop over a wide age range. The common macroscopic findings were splenomegaly and enlargement of lymph nodes. Histologic and immunohistochemical analyses revealed that all cases were non-Hodgkin type and exhibited a T-cell phenotype, positive for CD3 but negative for CD20 and CD79a. The lymphomas exhibited diverse cellular morphologies and were subdivided into 3 types according to the World Health Organization classification. These included 3 cases of peripheral T-cell lymphoma, not otherwise specified; 1 case of T-cell prolymphocytic leukemia; and 1 case of an unclassifiable T-cell lymphoma. Positive signals were detected by in situ hybridization in 2 of the 4 examined cases using probes for the Epstein-Barr virus-encoded small RNA (EBER). Furthermore, the presence of M. fuscata lymphocryptovirus 2, a macaque homolog of Epstein-Barr virus, was demonstrated in EBER-positive cases by polymerase chain reaction amplification followed by direct sequencing. Immunohistochemistry using antibody to the Epstein-Barr virus-encoded nuclear antigen 2 was negative, even in the EBER-positive cases. The present study suggests that T-cell lymphoma is more common than B-cell lymphoma in Japanese macaques and that M. fuscata lymphocryptovirus 2 is present in some cases.

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“…It accounts for 7-10% of all non-Hodgkin's lymphomas diagnosed in East Asia and Latin America, but only 1% of such lymphomas among Caucasians (1)(2)(3). Among the risk factors for NKTL development, Epstein-Barr virus (EBV) latent infection has been shown to play an important role, and ENKTL is closely associated with EBV infection (4)(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

LMP1 promotes nasal NK/T-cell lymphoma cell function by eIF4E via NF-κB pathway

et al. 2015

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Abstract. Nasal natural killer T-cell lymphoma (NKTL) is a highly malignant tumor that is closely associated with EpsteinBarr virus (EBV) infection. Latent membrane protein 1 (LMP1) is encoded by EBV and plays an important role in EBV-induced cell transformation. Therefore, we assessed the function of LMP1 as a stimulant of NKTL progression and the underlying mechanism. A human EBV-positive NKTL cell line (SNK-6) was transfected with pcDNA3.1-LMP1, LV-LMP1 shRNA or LV-eukaryotic translation initiation factor 4E (eIF4E)-shRNA. Then, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to assess the proliferation of SNK-6 cells, and cell migration and invasion were analyzed by Transwell chamber assay. Flow cytometry was used to analyze the cell cycle and apoptosis. The results showed LMP1 was highly expressed in SNK-6 cells compared with control groups. Following pretreatment with LMP1 shRNA, the proliferation of SNK-6 cells was inhibited and resulted in a G0/G1 phase arrest. A reduction in invasion and migration was also observed. LMP1 silencing promoted cell apoptosis. Further mechanistic analysis suggested that LMP1 overexpression induced the expression of eIF4E, while eIF4E-shRNA dramatically attenuated the increase in cell proliferation, invasion, migration and the inhibition of apoptosis triggered by LMP-1 upregulation. Moreover, the effect of LMP1 on eIF4E expression was mediated by the NF-κB pathway. Therefore, this finding may provide a potential target against NKTL.

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EBV-Associated Lymphoproliferative Disorders: Classification and Treatment

Cited by 236 publications

References 71 publications

Immunotherapy against cancer-related viruses

Immunotherapy against cancer-related viruses

Characterization of Spontaneous Malignant Lymphomas in Japanese Macaques (Macaca fuscata)

LMP1 promotes nasal NK/T-cell lymphoma cell function by eIF4E via NF-κB pathway

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