|
| Status |
Public on Apr 22, 2017 |
| Title |
Single-cell profiling of tumor infiltrating T cells and macrophages [Nanostring] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
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
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| |
|
| 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)
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| |
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| Contributor(s) |
Dries R, Adeegbe DO, Yan L |
| Citation(s) |
28408401 |
| Submission date |
Apr 21, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Ruben Dries |
| E-mail(s) |
rubendries@gmail.com
|
| Organization name |
DFCI
|
| Department |
Computational Biology
|
| Lab |
Longwood Center
|
| Street address |
360 Longwood Ave
|
| City |
Boston |
| ZIP/Postal code |
02215 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL22364 |
nCounter Mouse PanCancer Immune Profiling Panel |
|
| Samples (12)
|
| GSM2585951 |
JQ1-treated T cells[DA_9_02.RCC] |
| GSM2585952 |
Ricolinostat-treated T cells[DA_12_03.RCC] |
| GSM2585953 |
Ricolinostat-treated T cells[DA_33_06.RCC] |
| GSM2585954 |
Vehicle-treated macrophages[DA_20_10.RCC] |
| GSM2585955 |
Vehicle-treated macrophages[DA_21_11.RCC] |
| GSM2585956 |
JQ1-treated macrophages[DA_15_7.RCC] |
| GSM2585957 |
JQ1-treated macrophages[DA_16_8.RCC] |
| GSM2585958 |
Ricolinostat-treated macrophages[DA_19_9.RCC] |
| GSM2585959 |
Ricolinostat-treated macrophages[DA_34_12.RCC] |
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| This SubSeries is part of SuperSeries: |
| GSE98049 |
Synergistic Immunostimulatory Effects and Therapeutic Benefit of Combined Histone Deacetylase and Bromodomain Inhibition in Non-small Cell Lung Cancer. |
|
| Relations |
| BioProject |
PRJNA383804 |
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