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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Autores principales:	Andrea Aran, Vicente Peg, Rosa Maria Rabanal, Cristina Bernadó, Esther Zamora, Elisa Molina, Yago A. Arribas, Joaquín Arribas, José Pérez, Carme Roura-Mir, Montserrat Carrascal, Javier Cortés, Mercè Martí
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Epstein–Barr virus B cells T cells breast cancer TCR—T-cell receptor Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/d7e27f34772049269cfa3d1b3c5e3466
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spelling	oai:doaj.org-article:d7e27f34772049269cfa3d1b3c5e34662021-11-16T07:47:11ZEpstein–Barr Virus+ B Cells in Breast Cancer Immune Response: A Case Report1664-322410.3389/fimmu.2021.761798https://doaj.org/article/d7e27f34772049269cfa3d1b3c5e34662021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.761798/fullhttps://doaj.org/toc/1664-3224EBV-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.Andrea AranVicente PegRosa Maria RabanalCristina BernadóEsther ZamoraElisa MolinaYago A. ArribasJoaquín ArribasJoaquín ArribasJoaquín ArribasJoaquín ArribasJosé PérezCarme Roura-MirMontserrat CarrascalJavier CortésJavier CortésMercè MartíFrontiers Media S.A.articleEpstein–Barr virusB cellsT cellsbreast cancerTCR—T-cell receptorImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Epstein–Barr virus B cells T cells breast cancer TCR—T-cell receptor Immunologic diseases. Allergy RC581-607
spellingShingle	Epstein–Barr virus B cells T cells breast cancer TCR—T-cell receptor Immunologic diseases. Allergy RC581-607 Andrea Aran Vicente Peg Rosa Maria Rabanal Cristina Bernadó Esther Zamora Elisa Molina Yago A. Arribas Joaquín Arribas Joaquín Arribas Joaquín Arribas Joaquín Arribas José Pérez Carme Roura-Mir Montserrat Carrascal Javier Cortés Javier Cortés Mercè Martí Epstein–Barr Virus+ B Cells in Breast Cancer Immune Response: A Case Report
description	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.
format	article
author	Andrea Aran Vicente Peg Rosa Maria Rabanal Cristina Bernadó Esther Zamora Elisa Molina Yago A. Arribas Joaquín Arribas Joaquín Arribas Joaquín Arribas Joaquín Arribas José Pérez Carme Roura-Mir Montserrat Carrascal Javier Cortés Javier Cortés Mercè Martí
author_facet	Andrea Aran Vicente Peg Rosa Maria Rabanal Cristina Bernadó Esther Zamora Elisa Molina Yago A. Arribas Joaquín Arribas Joaquín Arribas Joaquín Arribas Joaquín Arribas José Pérez Carme Roura-Mir Montserrat Carrascal Javier Cortés Javier Cortés Mercè Martí
author_sort	Andrea Aran
title	Epstein–Barr Virus+ B Cells in Breast Cancer Immune Response: A Case Report
title_short	Epstein–Barr Virus+ B Cells in Breast Cancer Immune Response: A Case Report
title_full	Epstein–Barr Virus+ B Cells in Breast Cancer Immune Response: A Case Report
title_fullStr	Epstein–Barr Virus+ B Cells in Breast Cancer Immune Response: A Case Report
title_full_unstemmed	Epstein–Barr Virus+ B Cells in Breast Cancer Immune Response: A Case Report
title_sort	epstein–barr virus+ b cells in breast cancer immune response: a case report
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/d7e27f34772049269cfa3d1b3c5e3466
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Epstein–Barr Virus+ B Cells in Breast Cancer Immune Response: A Case Report

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