Epstein-Barr virus+ B cells in breast cancer immune response: a case report

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

doi:http://dx.doi.org/10.3389/fimmu.2021.761798

Epstein-Barr virus+ B cells in breast cancer immune response: a case report

License

Citation

Aran A, Peg V, Rabanal RM, Bernadó C, Zamora E, Molina E, et al. Epstein-Barr virus+ B cells in breast cancer immune response: a case report. Front Immunol. 2021 Nov 16; 12: 761798. DOI: 10.3389/fimmu.2021.761798

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.