CBP/p300 Drives the Differentiation of Regulatory T Cells through Transcriptional and Non-Transcriptional Mechanisms.

Autor:	Castillo J; Department of Oncology Biomarker Development, Development Sciences, Genentech, Inc., South San Francisco, California., Wu E; Department of Oncology Biomarker Development, Development Sciences, Genentech, Inc., South San Francisco, California., Lowe C; Department of Bioanalytical Sciences, Development Sciences, Genentech, Inc., South San Francisco, California., Srinivasan S; Department of Oncology Biomarker Development, Development Sciences, Genentech, Inc., South San Francisco, California., McCord R; Department of Oncology Biomarker Development, Development Sciences, Genentech, Inc., South San Francisco, California., Wagle MC; Department of Oncology Biomarker Development, Development Sciences, Genentech, Inc., South San Francisco, California., Jayakar S; Department of Research Pathology, Genentech, Inc., South San Francisco, California., Edick MG; Department of Research Pathology, Genentech, Inc., South San Francisco, California., Eastham-Anderson J; Department of Research Pathology, Genentech, Inc., South San Francisco, California., Liu B; Department of Oncology Biomarker Development, Development Sciences, Genentech, Inc., South San Francisco, California., Hutchinson KE; Department of Oncology Biomarker Development, Development Sciences, Genentech, Inc., South San Francisco, California., Jones W; Q Solutions-EA Genomics, Morrisville, North Carolina., Stokes MP; Cell Signaling Technology, Inc., Danvers, Massachusetts., Tarighat SS; Department of Oncology Biomarker Development, Development Sciences, Genentech, Inc., South San Francisco, California., Holcomb T; Department of Oncology Biomarker Development, Development Sciences, Genentech, Inc., South San Francisco, California., Glibicky A; Department of Oncology Biomarker Development, Development Sciences, Genentech, Inc., South San Francisco, California., Romero FA; Department of Discovery Chemistry, Genentech, Inc., South San Francisco, California., Magnuson S; Department of Discovery Chemistry, Genentech, Inc., South San Francisco, California., Huang SA; Department of Oncology Biomarker Development, Development Sciences, Genentech, Inc., South San Francisco, California., Plaks V; Department of Bioanalytical Sciences, Development Sciences, Genentech, Inc., South San Francisco, California., Giltnane JM; Department of Research Pathology, Genentech, Inc., South San Francisco, California., Lackner MR; Department of Oncology Biomarker Development, Development Sciences, Genentech, Inc., South San Francisco, California., Mounir Z; Department of Oncology Biomarker Development, Development Sciences, Genentech, Inc., South San Francisco, California. zineb.mounir@mail.mcgill.ca.
Jazyk:	angličtina
Zdroj:	Cancer research [Cancer Res] 2019 Aug 01; Vol. 79 (15), pp. 3916-3927. Date of Electronic Publication: 2019 Jun 10.
DOI:	10.1158/0008-5472.CAN-18-3622
Abstrakt:	Regulatory T cells (Treg) are immunosuppressive and negatively impact response to cancer immunotherapies. CREB-binding protein (CBP) and p300 are closely related acetyltransferases and transcriptional coactivators. Here, we evaluate the mechanisms by which CBP/p300 regulate Treg differentiation and the consequences of CBP/p300 loss-of-function mutations in follicular lymphoma. Transcriptional and epigenetic profiling identified a cascade of transcription factors essential for Treg differentiation. Mass spectrometry analysis showed that CBP/p300 acetylates prostacyclin synthase, which regulates Treg differentiation by altering proinflammatory cytokine secretion by T and B cells. Reduced Treg presence in tissues harboring CBP/p300 loss-of-function mutations was observed in follicular lymphoma. Our findings provide novel insights into the regulation of Treg differentiation by CBP/p300, with potential clinical implications on alteration of the immune landscape. SIGNIFICANCE: This study provides insights into the dynamic role of CBP/p300 in the differentiation of Tregs, with potential clinical implications in the alteration of the immune landscape in follicular lymphoma. (©2019 American Association for Cancer Research.)
Databáze:	MEDLINE
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