Transcriptomics,Genomics

Dataset Information

20

Single-cell profiling of tumor infiltrating T cells and macrophages [Nanostring]


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. Herein we evaluated the immunoregulatory properties of histone deacetylase (HDAC) and bromodomain inhibitors, two classes of drugs that modulate the epigenome, 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 that support enhanced T cell activation and improved 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 the immunomodulatory effects of two epigenetic modifiers that, together, promote T cell-mediated anti-tumor immunity and demonstrate their therapeutic potential for treatment of NSCLC. 6 Kras-mutant/p53-deficient lung tumors T cells and macrophages were analyzed wth Nanostring mouse PanCancer immune module Overall design: Gene expression analyses of tumor-infiltrating T cells and macrophages in lung tumor-bearing mice treated with Vehicle (control), ricolinostat (HDAC inhibitor), or JQ1 (Bromodomain inhibitor)

INSTRUMENT(S): nCounter Mouse PanCancer Immune Profiling Panel

SUBMITTER: Ruben Dries   

PROVIDER: GSE98044 | GEO | 2017-04-22

SECONDARY ACCESSION(S): PRJNA383804

REPOSITORIES: GEO

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Publications


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. Herein, we evaluated the immunoregulatory properties of histone deacetylase (HDAC) and bromodomain inhibitors, two classes of drugs that modulate the epigenome, with a focus on  ...[more]

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