دورية أكاديمية
IDH2 and TET2 mutations synergize to modulate T Follicular Helper cell functional interaction with the AITL microenvironment.
| العنوان: | IDH2 and TET2 mutations synergize to modulate T Follicular Helper cell functional interaction with the AITL microenvironment. |
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| المؤلفون: | Leca, J., Lemonnier, F., Meydan, C., Foox, J., El Ghamrasni, S., Mboumba, D.L., Duncan, G.S., Fortin, J., Sakamoto, T., Tobin, C., Hodgson, K., Haight, J., Smith, L.K., Elia, A.J., Butler, D., Berger, T., de Leval, L., Mason, C.E., Melnick, A., Gaulard, P., Mak, T.W. |
| المصدر: | Cancer cell, vol. 41, no. 2, pp. 323-339.e10 |
| سنة النشر: | 2023 |
| المجموعة: | Université de Lausanne (UNIL): Serval - Serveur académique lausannois |
| مصطلحات موضوعية: | Animals, Humans, Mice, Dioxygenases/genetics, DNA-Binding Proteins/genetics, Immunoblastic Lymphadenopathy/genetics, Isocitrate Dehydrogenase/genetics, Lymphoma, T-Cell/genetics, Mutation, T Follicular Helper Cells/pathology, T-Lymphocytes, Helper-Inducer, Tumor Microenvironment/genetics, Angioimmunoblastic T cell lymphoma, Idh2, T follicular helper cells, Tet2, cytokines, epigenetics, germinal center B cells, preclinical mouse model, therapeutic agents, tumor microenvironment |
| الوصف: | Angioimmunoblastic T cell lymphoma (AITL) is a peripheral T cell lymphoma that originates from T follicular helper (Tfh) cells and exhibits a prominent tumor microenvironment (TME). IDH2 and TET2 mutations co-occur frequently in AITL, but their contribution to tumorigenesis is poorly understood. We developed an AITL mouse model that is driven by Idh2 and Tet2 mutations. Malignant Tfh cells display aberrant transcriptomic and epigenetic programs that impair TCR signaling. Neoplastic Tfh cells bearing combined Idh2 and Tet2 mutations show altered cross-talk with germinal center B cells that promotes B cell clonal expansion while decreasing Fas-FasL interaction and reducing B cell apoptosis. The plasma cell count and angiogenesis are also increased in the Idh2-mutated tumors, implying a major relationship between Idh2 mutation and the characteristic AITL TME. Our mouse model recapitulates several features of human IDH2-mutated AITL and provides a rationale for exploring therapeutic targeting of Tfh-TME cross-talk for AITL patients. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1535-6108 |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/36736318; info:eu-repo/semantics/altIdentifier/eissn/1878-3686; info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_1FEDB421497F3; https://serval.unil.ch/notice/serval:BIB_1FEDB421497FTest; urn:issn:1535-6108; https://serval.unil.ch/resource/serval:BIB_1FEDB421497F.P001/REF.pdfTest; http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_1FEDB421497F3Test |
| DOI: | 10.1016/j.ccell.2023.01.003 |
| الإتاحة: | https://doi.org/10.1016/j.ccell.2023.01.003Test https://serval.unil.ch/notice/serval:BIB_1FEDB421497FTest https://serval.unil.ch/resource/serval:BIB_1FEDB421497F.P001/REF.pdfTest http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_1FEDB421497F3Test |
| حقوق: | info:eu-repo/semantics/openAccess ; CC BY-NC-ND 4.0 ; https://creativecommons.org/licenses/by-nc-nd/4.0Test/ |
| رقم الانضمام: | edsbas.72316123 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 15356108 |
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| DOI: | 10.1016/j.ccell.2023.01.003 |