IDH2 and TET2 mutations synergize to modulate T Follicular Helper cell functional interaction with the AITL microenvironment.

Details

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State: Public
Version: Final published version
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_1FEDB421497F
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
IDH2 and TET2 mutations synergize to modulate T Follicular Helper cell functional interaction with the AITL microenvironment.
Journal
Cancer cell
Author(s)
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.
ISSN
1878-3686 (Electronic)
ISSN-L
1535-6108
Publication state
Published
Issued date
13/02/2023
Peer-reviewed
Oui
Volume
41
Number
2
Pages
323-339.e10
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
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.
Keywords
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
Pubmed
Open Access
Yes
Create date
06/02/2023 12:59
Last modification date
31/05/2023 6:08
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