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

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 xen...

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Bibliographic Details
Published in:	Frontiers in immunology 2021-11, Vol.12, p.761798-761798
Main Authors:	Aran, Andrea, Peg, Vicente, Rabanal, Rosa Maria, Bernadó, Cristina, Zamora, Esther, Molina, Elisa, Arribas, Yago A, Arribas, Joaquín, Pérez, José, Roura-Mir, Carme, Carrascal, Montserrat, Cortés, Javier, Martí, Mercè
Format:	Article
Language:	eng
Subjects:	Adult Animals B cells B-Lymphocytes - immunology B-Lymphocytes - virology breast cancer Epstein–Barr virus Female Herpesvirus 4, Human - immunology Herpesvirus 4, Human - physiology HLA Antigens - immunology Humans Immunology Lymphocytes, Tumor-Infiltrating - immunology Lymphoma, B-Cell - immunology Mice Receptors, Antigen, T-Cell - immunology T cells TCR—T-cell receptor Triple Negative Breast Neoplasms - immunology
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Summary:	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.
ISSN:	1664-3224 1664-3224