Higher chemical complementarity of EBV epitopes and IGH CDR3s correlates with better outcomes for lymphoma and ovarian cancer

Madeline C Baker; Nandini Goel; Rahul Jain; Taha I Huda; Andrea Chobrutskiy; Boris I Chobrutskiy; Joanna J Song; Veda Naga Priya Vangala; Utsav Kapoor; George Blanck

doi:10.1007/s10552-025-02093-1

Higher chemical complementarity of EBV epitopes and IGH CDR3s correlates with better outcomes for lymphoma and ovarian cancer

Cancer Causes Control. 2025 Dec 27;37(1):13. doi: 10.1007/s10552-025-02093-1.

Authors

Affiliations

¹ Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA.
² Department of Pediatrics, Oregon Health and Science University Hospital, Portland, OR, 97239, USA.
³ Department of Internal Medicine, Oregon Health and Science University Hospital, Portland, OR, 97239, USA.
⁴ Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA. gblanck@usf.edu.
⁵ Department of Immunology, Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA. gblanck@usf.edu.
⁶ , 12901 Bruce B. Downs Bd. MDC7, Tampa, FL, 33612, USA. gblanck@usf.edu.

PMID: 41454997
DOI: 10.1007/s10552-025-02093-1

Abstract

This study investigated the relationship between Epstein-Barr virus (EBV) epitopes and tumor-resident immunoglobulin heavy chain (IGH) CDR3 amino acid (AA) sequences sourced from cancers with a link to EBV. In the case of ovarian cancer, the results revealed that higher chemical complementarity between certain EBV epitopes and IGH CDR3 AA sequences was linked to better outcomes. Additionally, IGH CDR3 and EBV epitope chemical complementarity was examined for Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL). For both BL and DLBCL, higher chemical complementarity to certain EBV epitopes was associated with improved overall survival probabilities. This latter result may be relevant to the occasional misdiagnosis of lymphoma for ovarian epithelial carcinoma. In sum, the results justify a more detailed study of the role of EBV and the anti-EBV immune response in the ovarian cancer and lymphoma settings.

Keywords: Complementarity-determining regions; Herpesvirus 4; Human; Immunoglobulin heavy chains; Lymphoma; Ovarian neoplasms; Survival.

MeSH terms

Burkitt Lymphoma / immunology
Burkitt Lymphoma / mortality
Burkitt Lymphoma / virology
Complementarity Determining Regions* / chemistry
Complementarity Determining Regions* / immunology
Epitopes* / chemistry
Epitopes* / immunology
Epstein-Barr Virus Infections* / complications
Epstein-Barr Virus Infections* / immunology
Epstein-Barr Virus Infections* / virology
Female
Herpesvirus 4, Human* / immunology
Humans
Immunoglobulin Heavy Chains* / chemistry
Immunoglobulin Heavy Chains* / genetics
Immunoglobulin Heavy Chains* / immunology
Lymphoma* / immunology
Lymphoma* / mortality
Lymphoma* / virology
Middle Aged
Ovarian Neoplasms* / immunology
Ovarian Neoplasms* / mortality
Ovarian Neoplasms* / virology
Prognosis

Substances

Immunoglobulin Heavy Chains
Epitopes
Complementarity Determining Regions