T cell-mediated immune surveillance conferred by latent Epstein-Barr virus genes suppresses a broad spectrum of tumor formation through NKG2D-NKG2DL interactions
Epstein-Barr virus (EBV)-infected B cells effectively induce T cell-mediated immune surveillance that suppresses the proliferation of EBV+ B cells and development of lymphomas. However, it remains unclear whether EBV-specific T cells are involved in the surveillance of EBV-negative general tumors. T...
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1597731/full |
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| author | Yuqi Jin Yun Guo Yohei Kawano Megumi Sasatani Shun Ohki Keita Yamane Yusei Ota Yumi Tamura Yusuke Sotomaru Yoshihiro Baba Tomoharu Yasuda |
| author_facet | Yuqi Jin Yun Guo Yohei Kawano Megumi Sasatani Shun Ohki Keita Yamane Yusei Ota Yumi Tamura Yusuke Sotomaru Yoshihiro Baba Tomoharu Yasuda |
| author_sort | Yuqi Jin |
| collection | DOAJ |
| description | Epstein-Barr virus (EBV)-infected B cells effectively induce T cell-mediated immune surveillance that suppresses the proliferation of EBV+ B cells and development of lymphomas. However, it remains unclear whether EBV-specific T cells are involved in the surveillance of EBV-negative general tumors. To address this issue, we induced immune surveillance by expressing key EBV antigens, LMP1 and LMP2A, in germinal center B cells and investigated the formation of non-B cell tumors. LMP1/2A mice showed a significantly reduced incidence of radiation-induced T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) even in the absence of LMP antigens in tumor cells and an extended life-span compared to control mice. LMP1/2A mice showed significantly higher numbers of activated memory T cells in both CD4+ and CD8+ αβT cell fractions compared to controls, suggesting their role in the elimination of tumor cells. Despite nearly absent MHC class I expression, tumor cells were effectively killed by CD8+ T cells activated upon LMP1/2A-expressing B cells. Transcriptome analysis identified upregulation of the NKG2D-NKG2DL pathway, emphasizing the capacity of LMP1/2A-induced T cells in the recognition of common tumor specific antigens. Moreover, not only T-cell tumors, but also intestinal tumors caused by ApcMin mutation were significantly suppressed by the LMP1/2A-induced immune surveillance. These results suggest that LMP1/2A-expression associated with EBV infection contributes to pan-tumor surveillance, implicating a beneficial aspect of EBV infection in humans and providing important insights into cancer prevention. |
| format | Article |
| id | doaj-art-3256173ebbb14013a16a07bbbce9a3ff |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-3256173ebbb14013a16a07bbbce9a3ff2025-08-20T03:07:21ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-06-011610.3389/fimmu.2025.15977311597731T cell-mediated immune surveillance conferred by latent Epstein-Barr virus genes suppresses a broad spectrum of tumor formation through NKG2D-NKG2DL interactionsYuqi Jin0Yun Guo1Yohei Kawano2Megumi Sasatani3Shun Ohki4Keita Yamane5Yusei Ota6Yumi Tamura7Yusuke Sotomaru8Yoshihiro Baba9Tomoharu Yasuda10Department of Immunology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, JapanDepartment of Immunology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, JapanDepartment of Immunology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, JapanDepartment of Experimental Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, JapanDepartment of Immunology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, JapanDepartment of Immunology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, JapanDepartment of Immunology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, JapanDepartment of Immunology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, JapanNatural Science Center for Basic Research and Development, Hiroshima University, Hiroshima, JapanDivision of Immunology and Genome Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, JapanDepartment of Immunology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, JapanEpstein-Barr virus (EBV)-infected B cells effectively induce T cell-mediated immune surveillance that suppresses the proliferation of EBV+ B cells and development of lymphomas. However, it remains unclear whether EBV-specific T cells are involved in the surveillance of EBV-negative general tumors. To address this issue, we induced immune surveillance by expressing key EBV antigens, LMP1 and LMP2A, in germinal center B cells and investigated the formation of non-B cell tumors. LMP1/2A mice showed a significantly reduced incidence of radiation-induced T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) even in the absence of LMP antigens in tumor cells and an extended life-span compared to control mice. LMP1/2A mice showed significantly higher numbers of activated memory T cells in both CD4+ and CD8+ αβT cell fractions compared to controls, suggesting their role in the elimination of tumor cells. Despite nearly absent MHC class I expression, tumor cells were effectively killed by CD8+ T cells activated upon LMP1/2A-expressing B cells. Transcriptome analysis identified upregulation of the NKG2D-NKG2DL pathway, emphasizing the capacity of LMP1/2A-induced T cells in the recognition of common tumor specific antigens. Moreover, not only T-cell tumors, but also intestinal tumors caused by ApcMin mutation were significantly suppressed by the LMP1/2A-induced immune surveillance. These results suggest that LMP1/2A-expression associated with EBV infection contributes to pan-tumor surveillance, implicating a beneficial aspect of EBV infection in humans and providing important insights into cancer prevention.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1597731/fullEpstein-Barr virusLMP1LMP2Aimmune surveillanceradiation-induced tumorT-ALL |
| spellingShingle | Yuqi Jin Yun Guo Yohei Kawano Megumi Sasatani Shun Ohki Keita Yamane Yusei Ota Yumi Tamura Yusuke Sotomaru Yoshihiro Baba Tomoharu Yasuda T cell-mediated immune surveillance conferred by latent Epstein-Barr virus genes suppresses a broad spectrum of tumor formation through NKG2D-NKG2DL interactions Frontiers in Immunology Epstein-Barr virus LMP1 LMP2A immune surveillance radiation-induced tumor T-ALL |
| title | T cell-mediated immune surveillance conferred by latent Epstein-Barr virus genes suppresses a broad spectrum of tumor formation through NKG2D-NKG2DL interactions |
| title_full | T cell-mediated immune surveillance conferred by latent Epstein-Barr virus genes suppresses a broad spectrum of tumor formation through NKG2D-NKG2DL interactions |
| title_fullStr | T cell-mediated immune surveillance conferred by latent Epstein-Barr virus genes suppresses a broad spectrum of tumor formation through NKG2D-NKG2DL interactions |
| title_full_unstemmed | T cell-mediated immune surveillance conferred by latent Epstein-Barr virus genes suppresses a broad spectrum of tumor formation through NKG2D-NKG2DL interactions |
| title_short | T cell-mediated immune surveillance conferred by latent Epstein-Barr virus genes suppresses a broad spectrum of tumor formation through NKG2D-NKG2DL interactions |
| title_sort | t cell mediated immune surveillance conferred by latent epstein barr virus genes suppresses a broad spectrum of tumor formation through nkg2d nkg2dl interactions |
| topic | Epstein-Barr virus LMP1 LMP2A immune surveillance radiation-induced tumor T-ALL |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1597731/full |
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