Abstract 3682: Synergistic immunostimulatory effects and therapeutic benefit of combined histone deacetylase and bromodomain inhibition in non-small cell lung cancer

Abstract

Abstract Effective therapies for non-small cell lung cancer (NSCLC) remain challenging despite an increasingly comprehensive understanding of somatically altered oncogenic pathways. It is now clear that therapeutic agents with potential to impact the tumor immune microenvironment potentiate immune-orchestrated therapeutic benefit. This study evaluated the immunoregulatory properties of two classes of drugs that modulate the epigenome, histone deacetylase (HDAC) and bromodomain inhibitors with a focus on key cell subsets that are engaged in an immune response. By evaluating human peripheral blood and NSCLC tumors, we show that the selective HDAC6 inhibitor ricolinostat promotes phenotypic changes associated with enhanced T-cell priming and function of antigen presenting cells. The bromodomain inhibitor JQ1 attenuated CD4+Foxp3+ T regulatory cell suppressive function and synergized with ricolinostat to facilitate immune-mediated tumor growth arrest, leading to prolonged survival of mice with lung adenocarcinomas. Collectively, our findings highlight immunomodulatory effects of two epigenetic modifiers that together promote T-cell-mediated anti-tumor immunity and demonstrate their therapeutic potential for NSCLC treatment. Citation Format: Dennis O. Adeegbe, Yan Liu, Patrick Lizotte, Yusuke Kamihara, Mark Awad, David Barbie, Jerome Ritz, Simon Jones, Steven Quayle, Peter Hammerman, Kwok-Kin Wong. Synergistic immunostimulatory effects and therapeutic benefit of combined histone deacetylase and bromodomain inhibition in non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3682. doi:10.1158/1538-7445.AM2017-3682