Reducing TNF Receptor 2+ Regulatory T Cells via the Combined Action of Azacitidine and the HDAC Inhibitor, Panobinostat for Clinical Benefit in Acute Myeloid Leukemia Patients 

Govindaraj, C, Tan, P, Walker, P, Wei, A, Spencer, A and Plebanski, M 2014, 'Reducing TNF Receptor 2+ Regulatory T Cells via the Combined Action of Azacitidine and the HDAC Inhibitor, Panobinostat for Clinical Benefit in Acute Myeloid Leukemia Patients ', Clinical Cancer Research, vol. 20, no. 3, pp. 724-735.


Document type: Journal Article
Collection: Journal Articles

Title Reducing TNF Receptor 2+ Regulatory T Cells via the Combined Action of Azacitidine and the HDAC Inhibitor, Panobinostat for Clinical Benefit in Acute Myeloid Leukemia Patients 
Author(s) Govindaraj, C
Tan, P
Walker, P
Wei, A
Spencer, A
Plebanski, M
Year 2014
Journal name Clinical Cancer Research
Volume number 20
Issue number 3
Start page 724
End page 735
Total pages 12
Publisher American Association for Cancer Research
Abstract Epigenetic therapies have proven to be effective when used in combination for the treatment of acute myeloid leukemia (AML). We sought to determine whether the clinical benefit of the novel combination of epigenetic drugs, azacitidine and panobinostat, was associated with a reduction of regulatory T cells (Treg), which are key players in dampening effective antitumor immune responses. We demonstrate a marked and rapid effect of the combination therapy to selectively target and reduce Tregs, particularly the functional TNF receptor-2+ (TNFR2+) Tregs in AML. This reduction of TNFR2+ Tregs is correlated with clinical responses in a population of patients unfit for intensive chemotherapy. In addition to providing new insights into novel and relevant immunologic parameters that can be targeted therapeutically, these findings provide for the first time, proof-of-concept in vivo validation of the ability of epigenetic therapies to suppress Tregs in AML.
Subject Immunology not elsewhere classified
DOI - identifier 10.1158/1078-0432.CCR-13-1576
Copyright notice © 2014 American Association for Cancer Research.
ISSN 1078-0432
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