Academic Journal
Modeling NK-cell lymphoma in mice reveals its cell-of-origin and microenvironmental changes and identifies therapeutic targets.
| العنوان: | Modeling NK-cell lymphoma in mice reveals its cell-of-origin and microenvironmental changes and identifies therapeutic targets. |
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| المؤلفون: | Koya, J., Tanigawa, T., Mizuno, K., Kim, H., Ito, Y., Yuasa, M., Yamaguchi, K., Kogure, Y., Saito, Y., Shingaki, S., Tabata, M., Murakami, K., Chiba, K., Okada, A., Shiraishi, Y., Marouf, A., Liévin, R., Chaubard, S., Jaccard, A., Hermine, O., de Leval, L., Tournilhac, O., Damaj, G., Gaulard, P., Couronné, L., Yasui, T., Nakashima, K., Miyoshi, H., Ohshima, K., Kataoka, K. |
| المصدر: | Nature communications, vol. 15, no. 1, pp. 9106 |
| سنة النشر: | 2024 |
| المجموعة: | Université de Lausanne (UNIL): Serval - Serveur académique lausannois |
| مصطلحات موضوعية: | Animals, Killer Cells, Natural/immunology, Natural/metabolism, Mice, Tumor Microenvironment/immunology, Lymphoma, Extranodal NK-T-Cell/genetics, Extranodal NK-T-Cell/metabolism, Extranodal NK-T-Cell/virology, Extranodal NK-T-Cell/pathology, Humans, Proto-Oncogene Proteins c-myc/metabolism, Proto-Oncogene Proteins c-myc/genetics, Tumor Suppressor Protein p53/metabolism, Tumor Suppressor Protein p53/genetics, Knockout, Disease Models, Animal, Interferon-gamma/metabolism, Receptors, CXCR6/metabolism, CXCR6/genetics, Chemokine CXCL16/metabolism, Chemokine CXCL16/genetics, Herpesvirus 4, Human, Gene Expression Regulation, Neoplastic, Signal Transduction |
| الوصف: | Extranodal NK/T-cell lymphoma (ENKTCL) is an Epstein-Barr virus (EBV)-related neoplasm preferentially involving the upper aerodigestive tract. Here we show that NK-cell-specific Trp53 disruption in mice leads to the development of NK-cell lymphomas after long latency, which involve not only the hematopoietic system but also the salivary glands. Before tumor onset, Trp53 knockout causes extensive gene expression changes, resulting in immature NK-cell expansion, exclusively in the salivary glands. Both human and murine NK-cell lymphomas express tissue-resident markers, suggesting tissue-resident NK cells as their cell-of-origin. Murine NK-cell lymphomas show recurrent Myc amplifications and upregulation of MYC target gene signatures. EBV-encoded latent membrane protein 1 expression accelerates NK-cell lymphomagenesis and causes diverse microenvironmental changes, particularly myeloid propagation, through interferon-γ signaling. In turn, myeloid cells support tumor cells via CXCL16-CXCR6 signaling and its inhibition is effective against NK-cell tumors in vivo. Remarkably, KLRG1-expressing cells expand in the tumor and are capable of repopulating tumors in secondary recipients. Furthermore, targeting KLRG1 alone or combined with MYC inhibition using an eIF4 inhibitor is effective against NK-cell tumors. Therefore, our observations provide insights into the pathogenesis and highlight potential therapeutic targets, including CXCL16, KLRG1, and MYC, in ENKTCL, which can help improve its diagnostic and therapeutic strategies. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/39438472; info:eu-repo/semantics/altIdentifier/eissn/2041-1723; info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_D1BDDC7D96C01; https://serval.unil.ch/notice/serval:BIB_D1BDDC7D96C0; https://serval.unil.ch/resource/serval:BIB_D1BDDC7D96C0.P001/REF.pdf |
| DOI: | 10.1038/s41467-024-53376-1 |
| الاتاحة: | https://serval.unil.ch/notice/serval:BIB_D1BDDC7D96C0 https://doi.org/10.1038/s41467-024-53376-1 https://serval.unil.ch/resource/serval:BIB_D1BDDC7D96C0.P001/REF.pdf http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_D1BDDC7D96C01 |
| Rights: | info:eu-repo/semantics/openAccess ; CC BY-NC-ND 4.0 ; https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| رقم الانضمام: | edsbas.7E4125FB |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-024-53376-1 |
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