Association of Epstein-Barr virus infection with peripheral immune parameters and clinical outcome in advanced nasopharyngeal carcinoma

Tao, Dan; Huang, Qinwen; Ge, Changrong; Li, Qicheng; Li, Shujie; Weng, Kegui; Guo, Qishuai; Sui, Jiangdong; Wang, Can; Zhang, Xin; Wang, Ying

doi:10.1038/s41598-020-78892-0

Cited by 4 publications

(3 citation statements)

References 35 publications

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“…Based on the diverse immune escape strategies described, a link of EBV infection with disease progression and response to therapy including immunotherapies is obvious. EBV-positive NPCs have been associated with significantly worse survival compared to EBV-negative patients [299,300], which is due to the induction of an immune-suppressive TME. This is in line with many other different EBV-induced tumor types, in which the immune-suppressive TME has been correlated with the patient outcome.…”

Section: Clinical Relevance Of Ebv In Malignanciesmentioning

confidence: 99%

Epstein–Barr Virus—Associated Malignancies and Immune Escape: The Role of the Tumor Microenvironment and Tumor Cell Evasion Strategies

Bauer

Jasinski‐Bergner

Mandelboim

et al. 2021

Cancers

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The detailed mechanisms of Epstein–Barr virus (EBV) infection in the initiation and progression of EBV-associated malignancies are not yet completely understood. During the last years, new insights into the mechanisms of malignant transformation of EBV-infected cells including somatic mutations and epigenetic modifications, their impact on the microenvironment and resulting unique immune signatures related to immune system functional status and immune escape strategies have been reported. In this context, there exists increasing evidence that EBV-infected tumor cells can influence the tumor microenvironment to their own benefit by establishing an immune-suppressive surrounding. The identified mechanisms include EBV gene integration and latent expression of EBV-infection-triggered cytokines by tumor and/or bystander cells, e.g., cancer-associated fibroblasts with effects on the composition and spatial distribution of the immune cell subpopulations next to the infected cells, stroma constituents and extracellular vesicles. This review summarizes (i) the typical stages of the viral life cycle and EBV-associated transformation, (ii) strategies to detect EBV genome and activity and to differentiate various latency types, (iii) the role of the tumor microenvironment in EBV-associated malignancies, (iv) the different immune escape mechanisms and (v) their clinical relevance. This gained information will enhance the development of therapies against EBV-mediated diseases to improve patient outcome.

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Section: Clinical Relevance Of Ebv In Malignanciesmentioning

confidence: 99%

Epstein–Barr Virus—Associated Malignancies and Immune Escape: The Role of the Tumor Microenvironment and Tumor Cell Evasion Strategies

Bauer

Jasinski‐Bergner

Mandelboim

et al. 2021

Cancers

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“…Another in vitro study by Huo and colleagues demonstrated that the EBNA1 protein was actively involved in the recruitment of regulatory T cells (Treg) via the up-regulated expression of TGF-ß [ 20 ]. A study by Tao and colleagues investigated the association between circulating immune cell frequencies, EBV viral loads and clinical outcome and demonstrated a significant association between plasma EBV DNA positivity and CD8+ T-cell presence [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Frequency of Peripheral CD8+ T Cells Expressing Chemo-Attractant Receptors CCR1, 4 and 5 Increases in NPC Patients with EBV Clearance upon Radiotherapy

Mahajan

Balcıoğlu

Oostvogels

et al. 2023

Cancers

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Radiotherapy (RT) is the standard-of-care for Epstein–Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC), where the post-RT clearance of plasma EBV DNA is prognostic. Currently, it is not known whether the post-RT clearance of plasma EBV DNA is related to the presence of circulating T-cell subsets. Blood samples from NPC patients were used to assess the frequency of T-cell subsets relating to differentiation, co-signaling and chemotaxis. Patients with undetectable versus detectable plasma EBV DNA levels post-RT were categorized as clearers vs. non-clearers. Clearers had a lower frequency of PD1+CD8+ T cells as well as CXCR3+CD8+ T cells during RT compared to non-clearers. Clearers exclusively showed a temporal increase in chemo-attractant receptors CCR1, 4 and/or 5, expressing CD8+ T cells upon RT. The increase in CCR-expressing CD8+ T cells was accompanied by a drop in naïve CD8+ T cells and an increase in OX40+CD8+ T cells. Upon stratifying these patients based on clinical outcome, the dynamics of CCR-expressing CD8+ T cells were in concordance with the non-recurrence of NPC. In a second cohort, non-recurrence associated with higher quantities of circulating CCL14 and CCL15. Collectively, our findings relate plasma EBV DNA clearance post-RT to T-cell chemotaxis, which requires validation in larger cohorts.

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“…EBV appears to have a broad impact on tumor development through its ability to induce genetic changes that affect various cellular processes, such as cell proliferation, migration, invasion, epithelial–mesenchymal transition (EMT), and angiogenesis [ 10 , 11 , 12 , 13 , 14 , 15 ]. EBV even alters the immune infiltration of tumors [ 16 ], further emphasizing the broad and complex effects of EBV on cancer biology.…”

Section: Introductionmentioning

confidence: 99%

EBV-Associated Hub Genes as Potential Biomarkers for Predicting the Prognosis of Nasopharyngeal Carcinoma

Ding,

Zhang,

Ren

et al. 2023

Viruses

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This study aimed to develop a model using Epstein–Barr virus (EBV)-associated hub genes in order to predict the prognosis of nasopharyngeal carcinoma (NPC). Differential expression analysis, univariate regression analysis, and machine learning were performed in three microarray datasets (GSE2371, GSE12452, and GSE102349) collected from the GEO database. Three hundred and sixty-six EBV-DEGs were identified, 25 of which were found to be significantly associated with NPC prognosis. These 25 genes were used to classify NPC into two subtypes, and six genes (C16orf54, CD27, CD53, CRIP1, RARRES3, and TBC1D10C) were found to be hub genes in NPC related to immune infiltration and cell cycle regulation. It was shown that these genes could be used to predict the prognosis of NPC, with functions related to tumor proliferation and immune infiltration, making them potential therapeutic targets. The findings of this study could aid in the development of screening and prognostic methods for NPC based on EBV-related features.

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Association of Epstein-Barr virus infection with peripheral immune parameters and clinical outcome in advanced nasopharyngeal carcinoma

Cited by 4 publications

References 35 publications

Epstein–Barr Virus—Associated Malignancies and Immune Escape: The Role of the Tumor Microenvironment and Tumor Cell Evasion Strategies

Epstein–Barr Virus—Associated Malignancies and Immune Escape: The Role of the Tumor Microenvironment and Tumor Cell Evasion Strategies

Frequency of Peripheral CD8+ T Cells Expressing Chemo-Attractant Receptors CCR1, 4 and 5 Increases in NPC Patients with EBV Clearance upon Radiotherapy

EBV-Associated Hub Genes as Potential Biomarkers for Predicting the Prognosis of Nasopharyngeal Carcinoma

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