Epstein–Barr virus‐associated lymphomas decoded

Bednarska, Karolina; Chowdhury, Rakin; Tobin, Joshua W. D.; Swain, Fiona; Keane, Colm; Boyle, Stephen; Khanna, Rajiv; Gandhi, Maher K.

doi:10.1111/bjh.19255

Cited by 3 publications

(1 citation statement)

References 161 publications

(379 reference statements)

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“…Recognizing patients at high risk and selecting appropriate therapeutic regimens are essential. Epstein–Barr virus (EBV) is a ubiquitous DNA virus belonging to the gamma subfamily of herpesviruses, associated with several lymphoma subtypes, such as Burkitt's lymphoma (BL) and extranodal NK/T-cell lymphoma (ENKTL) (Bednarska et al 2024 ; Damania et al 2022 ; Lopez et al 2022 ; Xiong et al 2020 ). EBV-associated lymphomas are characterized by the presence of EBV-encoded RNA (EBER) in tumor tissue.…”

Section: Introductionmentioning

confidence: 99%

Role of plasma EBV-DNA load and EBER status on newly diagnosed peripheral T-cell lymphoma

Chen,

Zhou,

Cheng

et al. 2024

J Cancer Res Clin Oncol

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Purpose To explore the prognostic and therapeutic role of Epstein-Barr Virus (EBV) on peripheral T-cell lymphoma (PTCL). Methods Totally 262 newly diagnosed PTCL patients who were hospitalized from January 2014 to December 2022 were retrospectively enrolled. Molecular analysis included 31 eligible patients. EBV-encoded RNA (EBER) presence in tumor tissue and EBV DNA levels in patients at baseline (DNA1) and after 4 cycles of chemotherapy (DNA4) were assessed. Results Our findings revealed that the EBER-positive cohort exhibited significant differences compared to counterparts in overall survival (OS, P = 0.047) and progression-free survival (PFS, P = 0.009). Both DNA1 and DNA4 were significantly associated with inferior OS. Multivariate analysis demonstrated that DNA4 independently affected PTCL prognosis for OS (hazard ratio = 5.1617; 95% confidence interval 1.1017–24.1831; P = 0.037). Treatment with the cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus azacytidine regimen showed a better OS compared to CHOP or CHOP plus etoposide for patients with partially positive EBER and EBER positive statuses (P = 0.192), although the improvement was not statistically significant. This study delineated the genetic paradigm of PTCL, comparing genetic differences by EBV status and found that EBER partially positive plus positive patients were more likely to have DNMT3A (P = 0.002), RHOAG17V (P = 0.023), and TET2 mutations (P = 0.032). Conclusion EBER, DNA1, and DNA4 emerged as sensitive markers for prognosis. CHOP plus azacytidine might present a preferable option for PTCL patients with DNA methylation due to EBV infection.

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Section: Introductionmentioning

confidence: 99%

Role of plasma EBV-DNA load and EBER status on newly diagnosed peripheral T-cell lymphoma

Chen,

Zhou,

Cheng

et al. 2024

J Cancer Res Clin Oncol

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Intra‐tumoral and peripheral blood TIGIT and PD‐1 as immune biomarkers in nodular lymphocyte predominant Hodgkin lymphoma

Gunawardana,

Law,

Sabdia

et al. 2024

American J Hematol

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In classical Hodgkin lymphoma (cHL), responsiveness to immune‐checkpoint blockade (ICB) is associated with specific tumor microenvironment (TME) and peripheral blood features. The role of ICB in nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is not established. To gain insights into its potential in NLPHL, we compared TME and peripheral blood signatures between HLs using an integrative multiomic analysis. A discovery/validation approach in 121 NLPHL and 114 cHL patients highlighted >2‐fold enrichment in programmed cell death‐1 (PD‐1) and T‐cell Ig and ITIM domain (TIGIT) gene expression for NLPHL versus cHL. Multiplex imaging showed marked increase in intra‐tumoral protein expression of PD‐1+ (and/or TIGIT+) CD4+ T‐cells and PD‐1+CD8+ T‐cells in NLPHL compared to cHL. This included T‐cells that rosetted with lymphocyte predominant (LP) and Hodgkin Reed–Sternberg (HRS) cells. In NLPHL, intra‐tumoral PD‐1+CD4+ T‐cells frequently expressed TCF‐1, a marker of heightened T‐cell response to ICB. The peripheral blood signatures between HLs were also distinct, with higher levels of PD‐1+TIGIT+ in TH1, TH2, and regulatory CD4+ T‐cells in NLPHL versus cHL. Circulating PD‐1+CD4+ had high levels of TCF‐1. Notably, in both lymphomas, highly expanded populations of clonal TIGIT+PD‐1+CD4+ and TIGIT+PD‐1+CD8+ T‐cells in the blood were also present in the TME, indicating that immune‐checkpoint expressing T‐cells circulated between intra‐tumoral and blood compartments. In in vitro assays, ICB was capable of reducing rosette formation around LP and HRS cells, suggesting that disruption of rosetting may be a mechanism of action of ICB in HL. Overall, results indicate that further evaluation of ICB is warranted in NLPHL.

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Multimodal integration of clinic, pathology, and genomics for a rare diagnosis of EBV-positive primary mediastinal large B-cell lymphoma

Thiebaut,

Isnard,

Couronné

et al. 2024

Virchows Arch

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Epstein–Barr virus‐associated lymphomas decoded

Cited by 3 publications

References 161 publications

Role of plasma EBV-DNA load and EBER status on newly diagnosed peripheral T-cell lymphoma

Role of plasma EBV-DNA load and EBER status on newly diagnosed peripheral T-cell lymphoma

Intra‐tumoral and peripheral blood TIGIT and PD‐1 as immune biomarkers in nodular lymphocyte predominant Hodgkin lymphoma

Multimodal integration of clinic, pathology, and genomics for a rare diagnosis of EBV-positive primary mediastinal large B-cell lymphoma

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