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EBV-driven B cell outgrowth can occur during TIL expansion, and EBV-transformed B cells may exert immunomodulatory functions, potentially impacting TIL therapy efficacy and safety \u2014 areas that remain underexplored. Here, we characterized a spontaneously arising wild-type EBV-transformed B cell line, lcl_burn0214, established during ex vivo culture of a tumor specimen from a rectal cancer patient who was EBV-negative. The lcl_burn0214 cell line has undergone 70 passages and was confirmed as a monoclonal B cell line of patient origin via HLA genotyping, immunophenotyping (CD19, CD20), B cell receptor clonotype analysis. RNA-seq analysis revealed that lcl_burn0214\u2019s gene expression closely resembles that of lymphoblastoid cells (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u20090.88) rather than malignant B lymphomas. In immunocompromised mice, lcl_burn0214 exhibited limited tumorigenicity. Autologous TILs were negative for B cells and exhibited a strong interferon-gamma response in the ELISPOT assay during coculture with lcl_burn0214 or with the EBV peptide pool (1000\u20131800 spots per million of TILs). Our findings underscore the importance of monitoring TIL products for EBV-positive B cell contamination during manufacturing to ensure safety and therapeutic efficacy even for EBV-negative patients.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-29456-7","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T08:35:10Z","timestamp":1763973310000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Latent EBV reactivation drives aberrant B-cell proliferation during ex vivo tumor-infiltrating lymphocyte expansion from EBV-negative rectal cancer tumor tissue"],"prefix":"10.1038","volume":"15","author":[{"given":"Tatiana V.","family":"Petrova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria V.","family":"Kuznetzova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra V.","family":"Kanygina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liubov O.","family":"Skorodumova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor A.","family":"Ivanov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana A.","family":"Astrelina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana E.","family":"Varlamova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena A.","family":"Zerkalenkova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena I.","family":"Sharova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,24]]},"reference":[{"key":"29456_CR1","doi-asserted-by":"publisher","first-page":"1289313","DOI":"10.3389\/fimmu.2023.1289313","volume":"14","author":"DG Sausen","year":"2023","unstructured":"Sausen, D. 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