Dr Pilar Dominguez - Peter MacCallum Cancer Centre

Dr Pilar Dominguez - Peter MacCallum Cancer Centre

Location: 
Online
Start Time: 
Tue, 26/10/2021 - 1:00pm
End Time: 
Tue, 26/10/2021 - 1:30pm

Special Lecture hosted by Dr Lahiru Gangoda – Blood Cells & Blood Cancer division

Dr Pilar Dominguez

Senior Research Officer, Peter MacCallum Cancer Centre

Epigenetic activation of plasmacytoid dendritic cells drives therapeutic differentiation of acute myeloid leukaemias

 

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Including Q&A session

 

Recent studies have demonstrated that pharmacological de-regulation of epigenetic enzymes can mediate anti-tumour immune responses, apart from affecting tumor cell growth and proliferation. We have discovered a novel mechanism of immune regulation through the inhibition of histone deacetylases (HDACs). In genetically engineered models of AML, leukemia cell differentiation and therapeutic benefit mediated by the HDAC inhibitor panobinostat required activation of the type I interferon (IFN) signaling pathway. Plasmacytoid dendritic cells (pDCs) were identified as the cells producing type I IFN in response to panobinostat, through transcriptional activation of IFN genes concomitant with increased H3K27 acetylation at these loci. Depletion of pDCs abrogated panobinostat-mediated activation of type I IFN signaling in leukemia cells and impaired therapeutic efficacy, while combined treatment of panobinostat and recombinant IFNa improved therapeutic outcomes in mouse and human models.

 

These discoveries offer a new therapeutic approach for AML and demonstrate that epigenetic rewiring of pDCs enhances anti-tumor immunity, opening the possibility of exploiting this cell type as a new target for immunotherapy.

 

All welcome!