Submit to Cancers Review for Cancers Propose a Special Issue

Journal Menu

Journal Browser

Epstein–Barr Virus (EBV) Associated Cancers

Special Issue Editors
Special Issue Information
Keywords
Benefits of Publishing in a Special Issue
Published Papers

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Infectious Agents and Cancer".

Deadline for manuscript submissions: closed (31 March 2025) | Viewed by 23538

Share This Special Issue

Special Issue Editors

Dr. Mário Henrique Magalhães Barros

E-Mail Website
Guest Editor

Institute for Pathology, Klinikum Chemnitz, Flemmingstraße 2, 09116 Chemnitz, Germany
Interests: hematopathology; EBV-associated neoplasia; classical Hodgkin lymphoma

Dr. Paola A. Chabay

E-Mail Website
Guest Editor

Laboratory of Molecular Biology, Pathology Division, Multidisciplinary Institute for Investigation in Pediatric Pathologies (IMIPP-CONICET-GCBA), Ricardo Gutiérrez Children’s Hospital, Gallo 1330, Buenos Aires C1425EFD, Argentina
Interests: EBV-positive DLBCL lymphomas; plasmablastic lymphomas
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

It has been almost 60 years since the initial discovery that the Epstein-Barr virus (EBV) could be related to the pathogenesis of Burkitt's lymphoma in sub-Saharan Africa. However, despite all this time, many questions related to the pathogenesis of EBV-associated neoplasms still remain unanswered.

The association of EBV with some neoplasms, in particular classical Hodgkin lymphoma, plasmablastic lymphoma, EBV-positive nodal NK/T-cell lymphoma and nasopharyngeal carcinoma, has been well described.

Although EBV infects more than 90% of the world's population, only a few individuals will develop a neoplasm associated with this virus. It is estimated that approximately 200,000 new cases of EBV-associated tumours are diagnosed globally each year, which has led the International Agency for Research on Cancer (IARC) to consider it as a group 1 carcinogen.

This Special Issue welcomes original articles and reviews related to EBV-associated neoplasms, including but not limited to viral pathogenesis, tissue microenvironment modulation, molecular epidemiology, treatment and prognosis. Articles regarding EBV-associated lymphomas, nasopharyngeal carcinoma and gastric carcinoma are greatly appreciated.

We look forward to receiving your contributions.

Dr. Mário Henrique Magalhães Barros
Dr. Paola A. Chabay
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Epstein–Barr Virus (EBV)
cancers
lymphoma
nasopharyngeal carcinoma
gastric carcinoma

Benefits of Publishing in a Special Issue

Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (10 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

Jump to: Review

17 pages, 1283 KiB

Open AccessArticle

Association Between Epstein–Barr Virus Infection and PD-L1 Expression in Gastric Cancer: Prevalence, Clinicopathological Features, and Prognostic Implications

by Jirapat Wonglhow, Jarukit Tantipisit, Panu Wetwittayakhlang, Patrapim Sunpaweravong, Chirawadee Sathitruangsak, Kanet Kanjanapradit, Phatcharaporn Thongwatchara and Arunee Dechaphunkul

Cancers 2025, 17(9), 1492; https://doi.org/10.3390/cancers17091492 - 29 Apr 2025

Abstract

Background: Epstein–Barr virus-associated gastric cancer (EBVaGC) represents a distinct molecular subgroup with potential responsiveness to immunotherapy approved for programmed death-ligand 1 (PD-L1)-positive gastric cancer. This retrospective study aimed to assess the prevalence and association between EBVaGC and PD-L1 positivity among patients with gastric adenocarcinoma treated at a university hospital in Southern Thailand from January 2017 to October 2023. Methods: The EBV status of the patients and PD-L1 expression were determined using in situ hybridization and immunohistochemistry, respectively. Results: The prevalence of EBVaGC was 4.5% among 132 patients, whereas 9.1% of patients exhibited a PD-L1 combined positive score (CPS) of ≥1, with no significant association observed between them. EBVaGC was more prevalent in males, non-antral tumors, diffuse/mixed histologic subtypes, and poorly differentiated tumors. Median overall survival for patients with EBVaGC and PD-L1 CPS ≥ 1 was 9.48 and 14.19 months, respectively, compared with 10.32 and 9.79 months for those with non-EBVaGC (hazard ratio: 1.24; 95% CI: 0.50–3.04; p = 0.645) and PD-L1 CPS < 1 (hazard ratio: 0.82; 95% CI: 0.40–1.69; p = 0.590), respectively. Conclusions: Our findings revealed a low prevalence of EBVaGC and PD-L1 positivity in Thailand, with no significant association or survival impact observed. These findings highlight the regional variation in these biomarkers and support EBV as an independent biomarker from PD-L1. However, further research, particularly studies evaluating immunotherapy outcomes, is warranted to clarify the predictive and clinical significance of EBV in gastric cancer. Full article

(This article belongs to the Special Issue Epstein–Barr Virus (EBV) Associated Cancers)

► Show Figures

Figure 1

11 pages, 2196 KiB

Open AccessArticle

Epstein Barr Virus (EBV) Latent Membrane Protein 1 (LMP-1) Regulates Functional Markers in Intermediate and Non-Classical Monocytes

by Agustina Moyano, Ana Colado, María Eugenia Amarillo, Elena De Matteo, María Victoria Preciado, Mercedes Borge and Paola Chabay

Cancers 2024, 16(24), 4169; https://doi.org/10.3390/cancers16244169 - 14 Dec 2024

Viewed by 919

Abstract

Background: The Epstein–Barr virus (EBV) infects more than 90 percent of the human population. In pediatric patients, the innate immune response against EBV primary infection plays a key role. Monocytes and macrophages can have distinct functions depending on the microenvironment surrounding them. At least three monocyte subpopulations can be differentiated depending on membrane protein expression: classical (C, CD14++CD16−), intermediate (I, CD14++CD16+), and non-classical (NC, CD14+CD16++). They also modulate T and B lymphocyte activation/inhibition through the expression of costimulatory molecules such as CD80, CD86, and PD-L1. Yet, little is known about monocytes’ role in EBV infection. Methods: Peripheral blood and tonsil biopsies of EBV primary infected (PI) patients, healthy carriers (HCs), and patients undergoing reactivation (R) were studied. Results: Classical monocytes prevailed in all infectious statuses. Tonsillar CD163 positively correlated with CD163 expression in NC monocytes in HCs. PD-L1+ cells in the tonsil positively correlated with PD-L1 expression in NC monocytes. LMP-1 viral latent protein presented a positive correlation with PD-L1, CD163, and CD206 expression in the NC subpopulation. Conclusions: Our results evidence the predominant role of I and NC monocytes’ response against EBV infection. Furthermore, the viral oncoprotein LMP-1 could be involved in the expression of regulatory proteins in I and NC monocytes. Full article

(This article belongs to the Special Issue Epstein–Barr Virus (EBV) Associated Cancers)

► Show Figures

Figure 1

16 pages, 1698 KiB

Open AccessArticle

Functional Targets for Epstein-Barr Virus BART MicroRNAs in B Cell Lymphomas

by Devin N. Fachko, Bonnie Goff, Yan Chen and Rebecca L. Skalsky

Cancers 2024, 16(20), 3537; https://doi.org/10.3390/cancers16203537 - 19 Oct 2024

Cited by 1 | Viewed by 1712

Abstract

MicroRNAs are key post-transcriptional regulators of gene expression and their dysregulation is often linked to cancer. Epstein-Barr virus encodes 22 BamHI A Rightward Transcript (BART) miRNAs, which are expressed in nearly all EBV-associated cancers and implicated in viral pathogenesis. To investigate biological targets for BART miRNAs in B cell lymphomas, we performed a meta-analysis of publicly available Ago-CLIP datasets from EBV-positive Burkitt lymphomas (BLs), primary effusion lymphomas (PELs), AIDS-associated diffuse large B cell lymphomas (DLBCLs), and lymphoblastoid cell lines (LCLs). Our analysis focused on comparing targets of EBV BART miRNAs across the different types of transformed B cells. Using reporter assays, we then experimentally validated over 50 functional interactions between BART miRNAs and cellular protein-coding transcripts involved in activities such as B cell differentiation (PRDM1, IRF4, and MYC), cell cycle regulation (UHMK1, CDKN1A, MDM2, and NPAT), apoptosis (MCL1), signaling and intracellular trafficking (GAB1, SOS1, MAPK1, RAB11A, CAV1, and RANBP9), and tumor suppression (CCDC6). Moreover, ectopic BART miRNA expression in several EBV-negative BL cells induced transcriptional changes that may influence molecular signatures of EBV-associated BLs. Collectively, our findings reveal novel, functional interactions for BART miRNAs in lymphomas and provide insights into their roles in these B cell cancers. Full article

(This article belongs to the Special Issue Epstein–Barr Virus (EBV) Associated Cancers)

► Show Figures

Figure 1

24 pages, 4655 KiB

Open AccessArticle

Dihydrotestosterone Enhances MICA-Mediated Immune Responses to Epstein–Barr Virus-Associated Gastric Carcinoma

by Donghyun Seo, Hyeji Byun, Miyeon Cho, Sun Hee Lee, Sohyun Youn, Junho Lee, Inuk Jung, Hyosun Cho and Hyojeung Kang

Cancers 2024, 16(18), 3219; https://doi.org/10.3390/cancers16183219 - 21 Sep 2024

Cited by 1 | Viewed by 1239

Abstract

Background: Epstein–Barr virus-associated gastric carcinoma (EBVaGC) is a subset of gastric cancers linked to EBV infection. While the role of male hormones in cancers such as prostate, breast, and ovarian cancers is well-studied, their impact on EBVaGC remains less understood. This study aims to examine the effect of dihydrotestosterone (DHT) on EBVaGC, particularly focusing on its influence on the immune response. Methods: The study utilized the SNU719 EBVaGC cell line. Cells were treated with DHT to assess androgen receptor (AR) expression and the activation of signaling pathways, including NF-κB. The expression of MHC class I polypeptide-related sequence A (MICA) and its interaction with the NKG2D receptor on NK and T cells was evaluated. Cytotoxicity assays were conducted to determine DHT’s effect on NK and T cell-mediated cytotoxicity, and proinflammatory cytokine gene expression was analyzed. Results: DHT significantly increased AR expression in EBVaGC cells and activated the NF-κB pathway, which led to increased transcription of target genes such as MICA and EBNA1. These changes enhanced the interaction with receptors on NK and T cells, thereby boosting their cytotoxicity against EBVaGC cells. Importantly, DHT did not upregulate proinflammatory cytokine genes. Conclusion: DHT enhances the immune response against EBVaGC by upregulating MICA and activating NK and T cells. These findings suggest potential therapeutic strategies targeting androgen signaling to improve anti-tumor immunity in EBVaGC. Full article

(This article belongs to the Special Issue Epstein–Barr Virus (EBV) Associated Cancers)

► Show Figures

Figure 1

19 pages, 4859 KiB

Open AccessArticle

Activation of Epstein–Barr Virus’ Lytic Cycle in Nasopharyngeal Carcinoma Cells by NEO212, a Conjugate of Perillyl Alcohol and Temozolomide

by Hannah Hartman-Houstman, Steve Swenson, Radu O. Minea, Uttam K. Sinha, Ming-Fu Chiang, Thomas C. Chen and Axel H. Schönthal

Cancers 2024, 16(5), 936; https://doi.org/10.3390/cancers16050936 - 26 Feb 2024

Cited by 3 | Viewed by 2272

Abstract

The Epstein–Barr virus (EBV) is accepted as a primary risk factor for certain nasopharyngeal carcinoma (NPC) subtypes, where the virus persists in a latent stage which is thought to contribute to tumorigenesis. Current treatments are sub-optimal, and recurrence occurs in many cases. An alternative therapeutic concept is aimed at triggering the lytic cycle of EBV selectively in tumor cells as a means to add clinical benefit. While compounds able to stimulate the lytic cascade have been identified, their clinical application so far has been limited. We are developing a novel anticancer molecule, NEO212, that was generated by covalent conjugation of the alkylating agent temozolomide (TMZ) to the naturally occurring monoterpene perillyl alcohol (POH). In the current study, we investigated its potential to trigger the lytic cycle of EBV in NPC cells in vitro and in vivo. We used the established C666.1 cell line and primary patient cells derived from the brain metastasis of a patient with NPC, both of which harbored latent EBV. Upon treatment with NEO212, there was an increase in EBV proteins Zta and Ea-D, key markers of the lytic cycle, along with increased levels of CCAAT/enhancer-binding protein homologous protein (CHOP), a marker of endoplasmic reticulum (ER) stress, followed by the activation of caspases. These effects could also be confirmed in tumor tissue from mice implanted with C666.1 cells. Towards a mechanistic understanding of these events, we used siRNA-mediated knockdown of CHOP and inclusion of anti-oxidant compounds. Both approaches blocked lytic cycle induction by NEO212. Therefore, we established a sequence of events, where NEO212 caused reactive oxygen species (ROS) production, which triggered ER stress and elevated the levels of CHOP, which was required to stimulate the lytic cascade of EBV. Inclusion of the antiviral agent ganciclovir synergistically enhanced the cytotoxic impact of NEO212, pointing to a potential combination treatment for EBV-positive cancers which should be explored further. Overall, our study establishes NEO212 as a novel agent able to stimulate EBV’s lytic cycle in NPC tumors, with implications for other virus-associated cancers. Full article

(This article belongs to the Special Issue Epstein–Barr Virus (EBV) Associated Cancers)

► Show Figures

Figure 1

31 pages, 8372 KiB

Open AccessArticle

Could Immune Checkpoint Disorders and EBV Reactivation Be Connected in the Development of Hematological Malignancies in Immunodeficient Patients?

by Paulina Mertowska, Sebastian Mertowski, Konrad Smolak, Gabriela Kita, Katarzyna Guz, Aleksandra Kita, Marcin Pasiarski, Jolanta Smok-Kalwat, Stanisław Góźdź and Ewelina Grywalska

Cancers 2023, 15(19), 4786; https://doi.org/10.3390/cancers15194786 - 29 Sep 2023

Cited by 1 | Viewed by 1826

Abstract

Primary immunodeficiencies (PIDs) and secondary immunodeficiencies (SIDs) are characterized by compromised immune function, rendering individuals susceptible to infections and potentially influencing cancer development. Epstein–Barr virus (EBV), a widespread herpesvirus, has been linked to cancer, particularly in those with weakened immune systems. This study aims to compare selected immune parameters, focusing on immune checkpoint molecules (PD-1/PD-L1, CTLA-4/CD86, CD200R/CD200), and EBV reactivation in patients with chronic lymphocytic leukemia (CLL, a representative of SIDs) and common variable immunodeficiency (CVID, a representative of PIDs). We performed a correlation analysis involving patients diagnosed with CLL, CVID, and a healthy control group. EBV reactivation was assessed using specific antibody serology and viral load quantification. Peripheral blood morphology, biochemistry, and immunophenotyping were performed, with emphasis on T and B lymphocytes expressing immune checkpoints and their serum concentrations. Our findings revealed elevated EBV reactivation markers in both CLL and CVID patients compared with healthy controls, indicating increased viral activity in immunodeficient individuals. Furthermore, immune checkpoint expression analysis demonstrated significantly altered percentages of T and B lymphocytes expressing PD-1/PD-L1, CTLA-4/CD86, and CD200R/CD200 in CLL and CVID patients. This suggests a potential interplay between immune checkpoint dysregulation and EBV reactivation in the context of immunodeficiency. In conclusion, our study underscores the intricate relationship between immune dysfunction, EBV reactivation, and immune checkpoint modulation in the context of immunodeficiency-associated cancers. The altered expression of immune checkpoints, along with heightened EBV reactivation, suggests a potential mechanism for immune evasion and tumor progression. These findings provide insights into the complex interactions that contribute to cancer development in immunocompromised individuals, shedding light on potential therapeutic targets for improved management and treatment outcomes. Further investigations are warranted to elucidate the underlying mechanisms and to explore potential interventions to mitigate cancer risk in these patient populations. Full article

(This article belongs to the Special Issue Epstein–Barr Virus (EBV) Associated Cancers)

► Show Figures

Figure 1

Review

Jump to: Research

28 pages, 2428 KiB

Open AccessEditor’s ChoiceReview

Epigenetic Mechanisms in Latent Epstein-Barr Virus Infection and Associated Cancers

by Atharva S. Torne and Erle S. Robertson

Cancers 2024, 16(5), 991; https://doi.org/10.3390/cancers16050991 - 29 Feb 2024

Cited by 11 | Viewed by 5324

Abstract

The Epstein–Barr Virus (EBV) is a double-stranded DNA-based human tumor virus that was first isolated in 1964 from lymphoma biopsies. Since its initial discovery, EBV has been identified as a major contributor to numerous cancers and chronic autoimmune disorders. The virus is particularly efficient at infecting B-cells but can also infect epithelial cells, utilizing an array of epigenetic strategies to establish long-term latent infection. The association with histone modifications, alteration of DNA methylation patterns in host and viral genomes, and microRNA targeting of host cell factors are core epigenetic strategies that drive interactions between host and virus, which are necessary for viral persistence and progression of EBV-associated diseases. Therefore, understanding epigenetic regulation and its role in post-entry viral dynamics is an elusive area of EBV research. Here, we present current outlooks of EBV epigenetic regulation as it pertains to viral interactions with its host during latent infection and its propensity to induce tumorigenesis. We review the important epigenetic regulators of EBV latency and explore how the strategies involved during latent infection drive differential epigenetic profiles and host-virus interactions in EBV-associated cancers. Full article

(This article belongs to the Special Issue Epstein–Barr Virus (EBV) Associated Cancers)

► Show Figures

Figure 1

23 pages, 1738 KiB

Open AccessReview

Precision Medicine for Nasopharyngeal Cancer—A Review of Current Prognostic Strategies

by Luvita Suryani, Hazel P. Y. Lee, Wei Keat Teo, Zhi Kang Chin, Kwok Seng Loh and Joshua K. Tay

Cancers 2024, 16(5), 918; https://doi.org/10.3390/cancers16050918 - 24 Feb 2024

Cited by 7 | Viewed by 3256

Abstract

Nasopharyngeal carcinoma (NPC) is an Epstein–Barr virus (EBV) driven malignancy arising from the nasopharyngeal epithelium. Current treatment strategies depend on the clinical stage of the disease, including the extent of the primary tumour, the extent of nodal disease, and the presence of distant metastasis. With the close association of EBV infection with NPC development, EBV biomarkers have shown promise in predicting treatment outcomes. Among the omic technologies, RNA and miRNA signatures have been widely studied, showing promising results in the research setting to predict treatment response. The transformation of radiology images into measurable features has facilitated the use of radiomics to generate predictive models for better prognostication and treatment selection. Nonetheless, much of this work remains in the research realm, and challenges remain in clinical implementation. Full article

(This article belongs to the Special Issue Epstein–Barr Virus (EBV) Associated Cancers)

► Show Figures

Figure 1

15 pages, 845 KiB

Open AccessReview

Modulation of Epstein-Barr-Virus (EBV)-Associated Cancers by Co-Infections

by Christian Münz

Cancers 2023, 15(24), 5739; https://doi.org/10.3390/cancers15245739 - 7 Dec 2023

Cited by 1 | Viewed by 2941

Abstract

The oncogenic and persistent Epstein Barr virus (EBV) is carried by more than 95% of the human adult population. While asymptomatic in most of these, EBV can cause a wide variety of malignancies of lymphoid or epithelial cell origin. Some of these are also associated with co-infections that either increase EBV-induced tumorigenesis or weaken its immune control. The respective pathogens include Kaposi-sarcoma-associated herpesvirus (KSHV), Plasmodium falciparum and human immunodeficiency virus (HIV). In this review, I will discuss the respective tumor entities and possible mechanisms by which co-infections increase the EBV-associated cancer burden. A better understanding of the underlying mechanisms could allow us to identify crucial features of EBV-associated malignancies and defects in their immune control. These could then be explored to develop therapies against the respective cancers by targeting EBV and/or the respective co-infections with pathogen-specific therapies or vaccinations. Full article

(This article belongs to the Special Issue Epstein–Barr Virus (EBV) Associated Cancers)

► Show Figures

Figure 1

18 pages, 12444 KiB

Open AccessReview

A Clinicopathology Review and Update of Epstein–Barr Virus-Associated Mesenchymal Tumors

by Oswald Zhao Jian Lee, Noorjehan Omar, Joshua K. Tay and Victor Kwan Min Lee

Cancers 2023, 15(23), 5563; https://doi.org/10.3390/cancers15235563 - 24 Nov 2023

Cited by 6 | Viewed by 3155

Abstract

The Epstein–Barr virus (EBV) is associated with various tumor types, including nasopharyngeal carcinoma and lymphoproliferative disorders. While much is known about EBV-related epithelial and lymphoid tumors, there is a paucity of knowledge concerning EBV-associated mesenchymal tumors. This review aims to provide a comprehensive overview of EBV-associated mesenchymal tumors, encompassing their clinical features, pathological characteristics, pathophysiology, prognostic factors, and current treatment approaches. Through an extensive literature search using the PubMed database, we were able to identify three distinct EBV-associated mesenchymal tumors: EBV-associated smooth muscle tumors, inflammatory pseudotumor-like follicular dendritic cell sarcomas, and EBV-associated osteosarcomas. Although this review extensively explored the different aspects of these mesenchymal tumors, our comprehension of the underlying pathophysiology in this context is still incomplete. Therefore, we hope that this review paper will not only serve as a valuable repository of information but also serve as a catalyst for prospective in vitro and in vivo research studies to bridge the existing knowledge gap surrounding pathophysiology, ultimately making an important contribution to shaping future therapeutic approaches. Full article

(This article belongs to the Special Issue Epstein–Barr Virus (EBV) Associated Cancers)

► Show Figures

Journal Menu

Journal Browser

Epstein–Barr Virus (EBV) Associated Cancers

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (10 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI