| Literature DB >> 29398449 |
Jose R Cortes1, Alberto Ambesi-Impiombato1, Lucile Couronné2, S Aidan Quinn1, Christine S Kim1, Ana C da Silva Almeida1, Zachary West1, Laura Belver1, Marta Sanchez Martin1, Laurianne Scourzic3, Govind Bhagat4, Olivier A Bernard3, Adolfo A Ferrando5, Teresa Palomero6.
Abstract
Angioimmunoblastic T cell lymphoma (AITL) is an aggressive tumor derived from malignant transformation of T follicular helper (Tfh) cells. AITL is characterized by loss-of-function mutations in Ten-Eleven Translocation 2 (TET2) epigenetic tumor suppressor and a highly recurrent mutation (p.Gly17Val) in the RHOA small GTPase. Yet, the specific role of RHOA G17V in AITL remains unknown. Expression of Rhoa G17V in CD4+ T cells induces Tfh cell specification; increased proliferation associated with inducible co-stimulator (ICOS) upregulation and increased phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase signaling. Moreover, RHOA G17V expression together with Tet2 loss resulted in development of AITL in mice. Importantly, Tet2-/-RHOA G17V tumor proliferation in vivo can be inhibited by ICOS/PI3K-specific blockade, supporting a driving role for ICOS signaling in Tfh cell transformation.Entities:
Keywords: ICOS; RHOA G17V; T follicular helper cells; TET2; angioimmunoblastic T cell lymphoma
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Year: 2018 PMID： 29398449 PMCID： PMC5811310 DOI： 10.1016/j.ccell.2018.01.001
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743