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

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

Cancer research (2019-06-12)
Joseph Castillo, Esther Wu, Christopher Lowe, Shrividhya Srinivasan, Ron McCord, Marie-Claire Wagle, Sangeeta Jayakar, Melissa Gonzalez Edick, Jeffrey Eastham-Anderson, Bonnie Liu, Katherine E Hutchinson, Wendell Jones, Matthew P Stokes, Somayeh S Tarighat, Thomas Holcomb, Andrew Glibicky, F Anthony Romero, Steven Magnuson, Shih-Min A Huang, Vicki Plaks, Jennifer M Giltnane, Mark R Lackner, Zineb Mounir
ANOTACE

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.

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