A mi familia, c-Myc Avian Myelocytomatosis virus oncogen Cellular homolog CAF Cyclophosphamide, doxorubicin, 5-fluoracil CBP/p300 CREB-Binding Protein/E1A binding protein p300 CCNE1 Cyclin E1 viii CD Cluster of Differentiation CD28 Cluster of Differentiation 28 CD60 Cluster of Differentiation 60 CD80 Cluster of Differentiation 80 CD86 Cluster of Differentiation 86 CDIS Carcinoma Ductal In Situ Cdk Cycling-dependent Kinase CDK1 Cycling-dependent Kinase 1 CEA Carcinoembrionic Antigen cFLIP cellular FLICE (FADD-like IL-1βconverting enzyme)-Like Inhibitor Protein CHECK2 CHK2 checkpoint homolog CHK2 Checkpoint Kinase 2

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 IIpresented 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 tumorinfiltrating T cells and influence the TCR repertoire in the tumor site.