Association of immunoescape mechanisms with Epstein‐Barr virus infection in nasopharyngeal carcinoma

Ogino, Takeshi; Moriai, Shigetaka; Ishida, Yoshiya; Ishii, Hidenori; Katayama, Akihiro; Miyokawa, Naoyuki; Harabuchi, Yasuaki; Ferrone, Soldano

doi:10.1002/ijc.22334

Cited by 43 publications

(34 citation statements)

References 41 publications

(50 reference statements)

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“…One report in 2007 showed that the HLA class I antigen expression was significantly lower in stages III and IV patients compared to that of stages I and II NPC patients. 25 Our results were not consistent with this observation maybe due to most of our patients were in stages III and IV (82%, 46/56).…”

Section: Discussioncontrasting

confidence: 70%

“…While, other reports also found that EBV infection of NPC tumor cells could downregulate HLA class I antigen expression compared to EBV negative benign nasopharyngeal epithelial. 25 However, it has also been demonstrated that EBV positive NPC tumor cells could be recognized by autologous EBV specific CTLs in vitro; and the antigen proceeding and presenting system is intact in NPC tumor cell lines in previous research. 60,61 These founding provide the possibility of success for immunotherapy in some NPC patients who have intact antigen proceeding and presenting systems in tumor cells.…”

Section: Discussionmentioning

confidence: 98%

“…Engagement of T cell receptor (TCR) by peptide-MHC complexes without co-stimulatory molecules results in profoundly anergic T cells that are unable to respond to further activation. 8,[21][22][23][24][25][26][27][28][29][30][31][32] It is therefore necessary to evaluate the expression pattern of these immune related molecules in tumor cell for further understanding the mechanism of tumor immune evasion and tumor development, and for identification of immunotherapeutic targets.…”

mentioning

confidence: 99%

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Expression of immune-related molecules in primary EBV positive chinese nasopharyngeal carcinoma: Associated with latent membrane protein 1 (LMP1) expression

Li¹,

Zhang²,

Xie³

et al. 2007

Cancer Biology & Therapy

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To understand the role of Epstein-Barr virus (EBV) and viral products in associated with immunophenotype and clinical outcome of primary nasopharyngeal carcinoma (NPC), the expression levels of chemokines IFN-g-induced protein 10 (IP-10, CXCL10), stromal-derived factor-1 (SDF-1, CXCL12) and its receptor CXCR4 was investigated in 56 primary NPC biopsy specimens from Chinese NPC patients in parallels with LMP1 antigen and EBER1 by immunohistochemisty (IHC) and in situ hybridization (ISH). Moreover, the expression levels of HLA class I (b-microglobulin) and II antigen (HLA-DR), and co-stimulatory molecule CD54 were also evaluated in 31 out of these 56 patients using immunohistochemisty (IHC). Our results showed that (a) the elevated expression levels of IP10, SDF-1, CXCR4, b-microglobulin, HLA-DR and CD54 in NPC lesions was 66%, 36%, 30%, 42%, 55% and 69%, respectively. The differentiated nonkeratinizing and undifferentiated types of nasopharyngeal carcinoma (NPC) are associated with Epstein-Barr virus (EBV) in South China, which has the highest incidence rate in the world. 1 The EBV latent type II antigens include nuclear antigen 1 (EBNA1), and latent membrane protein 1 (LMP1, in approximately 50%, seen in ref.2) and protein 2 (LMP2), in addition small non-polyadenylated viral RNAs non-coding nuclear RNAs (EBERs) and BamHI-A rightward transcripts (BARTs) expressed in NPC tumor cells. The expressions of EBV antigens in NPC tumor cells provide the targets for adoptive immunotherapy. [3][4][5][6] However, the poorly differentiated NPC is always characterized by the presence of a highly cellular lymphoid stroma admixed with tumor cells. 7 However, the role of local immunity surrounding NPC cells and the role EBV and viral products expressed in tumor cell remain unclear, which is associated with the expression of immune-related molecules including chemokines and receptors, HLA class I and II antigens, and co-stimulatory molecules and the role of EBV and viral products to alter the expression of immune-related molecules on tumor cells. It has been reported that the expression pattern of immune related-molecules on tumor cells will affect the outcome of T-cell-based adoptive immunotherapy for NPC. [8][9][10] In the tumor bed, chemokines and cytokines are secreted by both tumor-infiltrating immune cells and the tumor cells, and these chemokines and cytokines are capable of pleiotropic effects. 8 For example, IP-10 is a CXC chemokine produced by endothelial cells and macrophages post-stimulated by IFNg. IP-10 can induce rapid and transient adhesion of human IL-2-stimulated T lymphocytes to endothelial cells through its receptor CXCR3, which is selectively expressed on activated T cells. It is thought that expression of IP-10 in tumor cells induces potent anti-tumor functions, such as induction of the Th1 immune response and inhibition of angiogenesis. 11-13 SDF-1 is a a-chemokine, and bind to the only receptor CXCR4. Recent studies suggested that the SDF-1/CXCR4 axis play an important and unique role not only in th...

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Section: Discussioncontrasting

confidence: 70%

Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

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Expression of immune-related molecules in primary EBV positive chinese nasopharyngeal carcinoma: Associated with latent membrane protein 1 (LMP1) expression

Li¹,

Zhang²,

Xie³

et al. 2007

Cancer Biology & Therapy

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“…It plays a central role in the physiologic regulation of programmed cell death and has been implicated in the pathogenesis of various malignancies and diseases of the immune system. Fas ligand overexpression is an unfavorable prognostic marker in NPC (46,47).…”

Section: The Inferred Npc Network Consists Of Highly Interactive Cliqmentioning

confidence: 99%

From NPC Therapeutic Target Identification to Potential Treatment Strategy

Lan

Chen

Lin

et al. 2010

Molecular Cancer Therapeutics

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Nasopharyngeal carcinoma (NPC) is relatively rare in Western countries but is a common cancer in southern Asia. Many differentially expressed genes have been linked to NPC; however, how to prioritize therapeutic targets and potential drugs from unsorted gene lists remains largely unknown. We first collected 558 upregulated and 993 downregulated NPC genes from published microarray data and the primary literatures. We then postulated that conversion of gene signatures into the protein-protein interaction network and analyzing the network topologically could provide insight into key regulators involved in tumorigenesis of NPC. Of particular interest was the presence of cliques, called fully connected subgraphs, in the inferred NPC networks. These clique-based hubs, connecting with more than three queries and ranked higher than other nodes in the NPC protein-protein interaction network, were further narrowed down by pathway analysis to retrieve 24 upregulated and 6 downregulated bottleneck genes for predicting NPC carcinogenesis. Moreover, additional oncogenes, tumor suppressor genes, genes involved in protein complexes, and genes obtained after functional profiling were merged with the

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“…Clinical studies with nasopharyngeal carcinoma (NPC) lesions during EBV infection suggest that LMP2, TAP1, tapasin and HLA class I antigens are downregulated [105].…”

Section: Regulation Of Tap and Tapasinmentioning

confidence: 99%

Immune Regulation and Evasion of Mammalian Host Cell Immunity During Viral Infection

et al. 2013

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The mammalian host immune system has wide array of defence mechanisms against viral infections. Depending on host immunity and the extent of viral persistence, either the host immune cells might clear/restrict the viral load and disease progression or the virus might evade host immunity by down regulating host immune effector response(s). Viral antigen processing and presentation in the host cells through major histocompatibility complex (MHC) elicit subsequent anti-viral effector T cell response(s). However, modulation of such response(s) might generate one of the important viral immune evasion strategies. Viral peptides are mostly generated by proteolytic cleavage in the cytosol of the infected host cells. CD8 ? T lymphocytes play critical role in the detection of viral infection by recognizing these peptides displayed at the plasma membrane by MHC-I molecules. The present review summarises the current knowledge on the regulation of mammalian host innate and adaptive immune components, which are operative in defence mechanisms against viral infections and the variety of strategies that viruses have evolved to escape host cell immunity. The understanding of viral immune evasion strategies is important for designing anti-viral immunotherapies.

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Association of immunoescape mechanisms with Epstein‐Barr virus infection in nasopharyngeal carcinoma

Cited by 43 publications

References 41 publications

Expression of immune-related molecules in primary EBV positive chinese nasopharyngeal carcinoma: Associated with latent membrane protein 1 (LMP1) expression

Expression of immune-related molecules in primary EBV positive chinese nasopharyngeal carcinoma: Associated with latent membrane protein 1 (LMP1) expression

From NPC Therapeutic Target Identification to Potential Treatment Strategy

Immune Regulation and Evasion of Mammalian Host Cell Immunity During Viral Infection

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