Characterization of latently infected EBV+ antibody-secreting B cells isolated from ovarian tumors and malignant ascites.

Autor:	Zhang L; Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.; Magee-Womens Research Institute, Pittsburgh, PA, United States., Strange M; Magee-Womens Research Institute, Pittsburgh, PA, United States., Elishaev E; Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.; Magee-Womens Hospital of University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, United States., Zaidi S; Magee-Womens Research Institute, Pittsburgh, PA, United States., Modugno F; Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.; Magee-Womens Research Institute, Pittsburgh, PA, United States., Radolec M; Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.; Magee-Womens Research Institute, Pittsburgh, PA, United States.; Magee-Womens Hospital of University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, United States., Edwards RP; Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.; Magee-Womens Research Institute, Pittsburgh, PA, United States.; Magee-Womens Hospital of University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, United States., Finn OJ; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States., Vlad AM; Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.; Magee-Womens Research Institute, Pittsburgh, PA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Jul 17; Vol. 15, pp. 1379175. Date of Electronic Publication: 2024 Jul 17 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1379175
Abstrakt:	Introduction: Intra-tumoral B cells mediate a plethora of immune effector mechanisms with key roles in anti-tumor immunity and serve as positive prognostic indicators in a variety of solid tumor types, including epithelial ovarian cancer (EOC). Several aspects of intra-tumoral B cells remain unclear, such as their state of activation, antigenic repertoires, and capacity to mature into plasma cells. Methods: B lymphocytes were isolated from primary EOC tissue and malignant ascites and were maintained in cell culture medium. The stably maintained cell lines were profiled with flow cytometry and B cell receptor sequencing. Secreted antibodies were tested with a human proteome array comprising more than 21,000 proteins, followed by ELISA for validation. Originating tumor samples were used for spatial profiling with chip cytometry. Results: Antibody-secreting B lymphocytes were isolated from the ovarian tumor microenvironment (TME) of four different EOC patients. The highly clonal cell populations underwent spontaneous immortalization in vitro , were stably maintained in an antibody-secreting state, and showed presence of Epstein-Barr viral (EBV) proteins. All originating tumors had high frequency of tumor-infiltrating B cells, present as lymphoid aggregates, or tertiary lymphoid structures. The antigens recognized by three of the four cell lines are coil-coil domain containing protein 155 (CCDC155), growth factor receptor-bound protein 2 (GRB2), and pyruvate dehydrogenase phosphatase2 (PDP2), respectively. Anti-CCDC155 circulating IgG antibodies were detected in 9 of 20 (45%) of EOC patients' sera. Tissue analyses with multiparameter chip cytometry shows that the antibodies secreted by these novel human B cell lines engage their cognate antigens on tumor cells. Discussion: These studies demonstrate that within the tumor-infiltrating lymphocyte population in EOC resides a low frequency population of antibody-secreting B cells that have been naturally exposed to EBV. Once stably maintained, these novel cell lines offer unique opportunities for future studies on intratumor B cell biology and new target antigen recognition, and for studies on EBV latency and/or viral reactivation in the TME of non-EBV related solid tumors such as the EOC. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Zhang, Strange, Elishaev, Zaidi, Modugno, Radolec, Edwards, Finn and Vlad.)
Databáze:	MEDLINE
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