Lymphocytic Infiltration in Undifferentiated Nasopharyngeal Cancer

Jayasurya, Anita; Bay, Boon‐Huat; Yap, Wai-Ming; Tan, Nam-Guan

doi:10.1001/archotol.126.11.1329

Cited by 17 publications

(13 citation statements)

References 29 publications

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“…Host immune responses toward persistent HBV infection may promote chronic inflammation and cell proliferation and subsequently induce oncogenic transformation of the infected cells (18)(19)(20). NPC tumor cells are known to be heavily infiltrated by lymphocytes (21). B lymphocytes can be infected by EBV and HBV simultaneously (22)(23)(24).…”

Section: Introductionmentioning

confidence: 99%

Hepatitis B Virus Infection and Risk of Nasopharyngeal Carcinoma in Southern China

Xiang

Fang

et al. 2015

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Whether or not hepatitis B virus (HBV) infection plays a role in the development of nasopharyngeal carcinoma (NPC) is largely unknown. Our study aimed to assess the association between HBV infection and the risk of NPC in Southern China.Methods: We conducted a case-control study including 711 NPC cases and two groups of controls. The first control group consisted of 656 individuals with other benign tumors unrelated to HBV infection and the second group consisted of 680 healthy population controls. Multivariable ORs and corresponding 95% confidence intervals (CI) for NPC were estimated by logistic regression.Results: Patients with NPC had higher prevalence of antibodies against hepatitis B core antigen-positive [anti-HBc-(þ); 47.26%] compared with either benign tumor controls (39.33%; P < 0.01)

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Section: Introductionmentioning

confidence: 99%

Hepatitis B Virus Infection and Risk of Nasopharyngeal Carcinoma in Southern China

Xiang

Fang

et al. 2015

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…M-CSF inhibition by secreted BARF1 might be instrumental for EBV in restricting maturation of macrophage effector functions, thus ensuring that these immune cells support dissemination of viral progeny rather than elimination of the internalized or bound virus. In NPC, lymphocyte infiltration does not affect prognosis (23,26), but infiltration of NPC with mononuclear cells is correlated with a higher survival rate (12,39), indicating their involvement in tumor cell eradication. An EBV-infected tumor cell, expressing viral antigens that can be recognized, might thus benefit from local myeloid suppression resulting from M-CSF inhibition by BARF1.…”

Section: Introductionmentioning

confidence: 99%

“…BARF1 was recently shown to trigger both CD4 and CD8 cellular immune responses in NPC patients, providing a basis for specific immunotherapy (29). However, the lymphocytes from the NPC tumor environment are functionally impaired (23,26). By binding and functionally inhibiting M-CSF, sBARF1 might interfere with myeloid sentinel functions, and thus contribute to an immunological silence facilitating immune escape.…”

Section: Introductionmentioning

confidence: 99%

Epstein-Barr Virus-Encoded BARF1 Protein is a Decoy Receptor for Macrophage Colony Stimulating Factor and Interferes with Macrophage Differentiation and Activation

et al. 2012

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Epstein-Barr virus (EBV), like many other persistent herpes viruses, has acquired numerous mechanisms for subverting or evading immune surveillance. This study investigates the role of secreted EBV-encoded BARF1 protein (sBARF1) in creating an immune evasive microenvironment. Wild-type consensus BARF1 was expressed in the human 293 cell line and purified. This native hexameric sBARF1 had inhibitory capacity on macrophage colony stimulating factor (M-CSF)-stimulated, and not on granulocyte macrophage-colony stimulating factor (GM-CSF)-stimulated growth and differentiation of myeloid cells. Antibodies specific to hexameric sBARF1 were able to block this effect. M-CSF was shown to interact with sBARF1 via the protruding N-terminal loops involving Val38 and Ala84. Each BARF1 hexamer was capable of binding three M-CSF dimers. Mutations in the BARF1 loops greatly affected M-CSF interaction, and showed loss of growth inhibition. Analysis of the activation state of the M-CSF receptor c-fms and its downstream kinase pathways showed that sBARF1 prevented M-CSF-induced downstream phosphorylation. Since M-CSF is an important factor in macrophage differentiation, the effect of sBARF1 on the function of monocyte-derived macrophages was evaluated. sBARF1 affected overall survival and morphology and significantly reduced expression of macrophage differentiation surface markers such as CD14, CD11b, CD16, and CD169. Macrophages differentiating in the presence of sBARF1 showed impaired responses to lipopolysaccharide and decreased oxygen radical formation as well as reduced phagocytosis of apoptotic cells. In conclusion, EBV sBARF1 protein is a potent decoy receptor for M-CSF, hampering the function and differentiation of macrophages. These results suggest that sBARF1 contributes to the modulation of immune responses in the microenvironment of EBV-positive carcinomas.

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“…NPC is strongly linked to consumption of Cantonese salted fish (Ning et al 1990) and infection with Epstein-Barr virus (EBV) (Raab-Traub 2002), which is almost invariably present within the cancer cells and is thought to promote oncogenic transformation (zur Hausen et al 1970). A challenging feature of NPC genome sequencing is that significant lymphocyte infiltration (e.g., 80% of cells in a sample) (Jayasurya et al 2000) is common, requiring special laboratory and bioinformatic approaches not necessary for higher-purity tumors (Mardis et al 2009). …”

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confidence: 99%

Discovery of recurrent structural variants in nasopharyngeal carcinoma

et al. 2013

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We present the discovery of genes recurrently involved in structural variation in nasopharyngeal carcinoma (NPC) and the identification of a novel type of somatic structural variant. We identified the variants with high complexity mate-pair libraries and a novel computational algorithm specifically designed for tumor-normal comparisons, SMASH. SMASH combines signals from split reads and mate-pair discordance to detect somatic structural variants. We demonstrate a >90% validation rate and a breakpoint reconstruction accuracy of 3 bp by Sanger sequencing. Our approach identified three in-frame gene fusions (YAP1-MAML2, PTPLB-RSRC1, and SP3-PTK2) that had strong levels of expression in corresponding NPC tissues. We found two cases of a novel type of structural variant, which we call ''coupled inversion,'' one of which produced the YAP1-MAML2 fusion. To investigate whether the identified fusion genes are recurrent, we performed fluorescent in situ hybridization (FISH) to screen 196 independent NPC cases. We observed recurrent rearrangements of MAML2 (three cases), PTK2 (six cases), and SP3 (two cases), corresponding to a combined rate of structural variation recurrence of 6% among tested NPC tissues.

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Lymphocytic Infiltration in Undifferentiated Nasopharyngeal Cancer

Abstract: The lymphoid infiltrate is beneficial in undifferentiated NPC, and its presence may deter regional metastasis of cancer cells to the cervical nodes.

Cited by 17 publications

References 29 publications

Hepatitis B Virus Infection and Risk of Nasopharyngeal Carcinoma in Southern China

Hepatitis B Virus Infection and Risk of Nasopharyngeal Carcinoma in Southern China

Epstein-Barr Virus-Encoded BARF1 Protein is a Decoy Receptor for Macrophage Colony Stimulating Factor and Interferes with Macrophage Differentiation and Activation

Discovery of recurrent structural variants in nasopharyngeal carcinoma

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