Better Outcomes for Ovarian Cancer Associated With the Detection of Anti-EBV TCR CDR3s: Potential Relevance to Diffuse Large B-Cell Lymphoma

Am J Reprod Immunol. 2025 Jan;93(1):e70046. doi: 10.1111/aji.70046.

Abstract

Objectives: Given the ongoing challenges regarding the specific roles of viral infections in cancer etiology, or as cancer co-morbidities, this study assessed potential associations between anti-viral, T-cell receptor (TCR) complementarity domain region-3 (CDR3s), and clinical outcomes for ovarian cancer.

Methods: TCR CDR3s were isolated from ovarian cancer specimens for a determination of which patients had anti-viral CDR3s and whether those patients had better or worse outcomes.

Results: Analyses revealed that patients with exact matches of anti-Epstein-Barr virus (EBV) CDR3 amino acid sequences exhibited better outcomes for both overall and disease-specific survival. However, better outcomes were not observed when assessing anti-viral CDR3s representing cytomegalovirus, influenza A, or Sars-CoV-2. Due to previous occurrences of the occasional misdiagnoses of lymphoma as ovarian cancer, the frequency of anti-EBV CDR3s in lymphoma patients was determined. These frequencies were relatively high, particularly for diffuse large B-cell lymphoma.

Conclusions: These findings (i) underscore the potential value of anti-EBV immune responses in terms of patient outcomes; (ii) raise questions about the potential value of anti-EBV immunotherapies; and (iii) support further inquiry into the relationship between EBV infection and previously reported cases of ovary-resident lymphoma.

Keywords: Epstein–Barr virus; TCR CDR3s; disease‐specific survival; ovarian cancer; overall survival.

MeSH terms

  • Adult
  • Aged
  • COVID-19 / immunology
  • Complementarity Determining Regions* / genetics
  • Complementarity Determining Regions* / immunology
  • Cytomegalovirus / immunology
  • Epstein-Barr Virus Infections / immunology
  • Female
  • Herpesvirus 4, Human* / immunology
  • Humans
  • Influenza A virus / immunology
  • Lymphoma, Large B-Cell, Diffuse* / immunology
  • Lymphoma, Large B-Cell, Diffuse* / virology
  • Middle Aged
  • Ovarian Neoplasms* / immunology
  • Receptors, Antigen, T-Cell* / immunology
  • Receptors, Antigen, T-Cell* / metabolism
  • SARS-CoV-2 / immunology

Substances

  • Complementarity Determining Regions
  • Receptors, Antigen, T-Cell