Epstein-Barr Virus+ B Cells in Breast Cancer Immune Response: A Case Report

Andrea Aran, Vicente Peg, Rosa Maria Rabanal Prados, Cristina Bernadó, Esther Zamora, Elisa Molina, Yago A Arribas, Joaquín Arribas, José Pérez, Carme Roura-Mir, Montserrat Carrascal, Javier Cortés, Mercè Martí

Research output: Contribution to journalArticleResearchpeer-review

Abstract

EBV-specific T cells have been recently described to be involved in fatal encephalitis and myocarditis in cancer patients after immune checkpoint therapies. Here, we report the study of a human triple-negative breast cancer tumor (TNBC) and EBV-transformed B cells obtained from a patient-derived xenograft (PDX) that progressed into a lymphocytic neoplasm named xenograft-associated B-cell lymphoma (XABCL). T-cell receptor (TCR) high-throughput sequencing was performed to monitor the T-cell clonotypes present in the different samples. Forty-three T-cell clonotypes were found infiltrating the XABCL tissue after three passes in mice along 6 months. Eighteen of these (42%) were also found in the TNBC biopsy. TCR infiltrating the XABCL tissue showed a very restricted T-cell repertoire as compared with the biopsy-infiltrating T cells. Consequently, T cells derived from the TNBC biopsy were expanded in the presence of the B-cell line obtained from the XABCL (XABCL-LCL), after which the TCR repertoire obtained was again very restricted, i.e., only certain clonotypes were selected by the B cells. A number of these TCRs had previously been reported as sequences involved in infection, cancer, and/or autoimmunity. We then analyzed the immunopeptidome from the XABCL-LCL, to identify putative B-cell-associated peptides that might have been expanding these T cells. The HLA class I and class II-associated peptides from XABCL-LCL were then compared with published repertoires from LCL of different HLA typing. Proteins from the antigen processing and presentation pathway remained significantly enriched in the XABCL-LCL repertoire. Interestingly, some class II-presented peptides were derived from cancer-related proteins. These results suggest that bystander tumor-infiltrating EBV+ B cells acting as APC may be able to interact with tumor-infiltrating T cells and influence the TCR repertoire in the tumor site.

Original languageEnglish
Pages (from-to)761798
JournalFrontiers in immunology
Volume12
DOIs
Publication statusPublished - 16 Nov 2021

Fingerprint

Dive into the research topics of 'Epstein-Barr Virus+ B Cells in Breast Cancer Immune Response: A Case Report'. Together they form a unique fingerprint.

Cite this