4.8 Article

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

Journal

FRONTIERS IN IMMUNOLOGY
Volume 12, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.761798

Keywords

Epstein-Barr virus; B cells; T cells; breast cancer; TCR-T-cell receptor

Categories

Funding

  1. Roche Farma, S. A. grant [SP181123001]
  2. Spanish Ministry of Science, Innovation and Universities grant [RTI2018-097414-B-I00]
  3. El Paseico de la Mama 2015
  4. Roche Farma, S.A.

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The study found a restricted T-cell repertoire in tumor tissue during xenograft progression, while T cells from the TNBC biopsy were expanded after transformation into B-cell line, resulting in a limited TCR repertoire. These results suggest that EBV+ B cells infiltrating the tumor as bystanders may interact with tumor-infiltrating T cells and influence the TCR repertoire.
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.

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