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| Status |
Public on Jun 14, 2021 |
| Title |
Innate and adaptive immunity cross-talk reprograms the tumor microenvironment to an inflammatory hub able to eliminate established poorly immunogenic tumors |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Clinical benefit remains elusive for most patients with poorly inflamed carcinomas treated with immune checkpoint blockade. Alternative therapies able to convert the tumor microenvironment (TME) into a functionally inflamed immune hub may increase clinical benefit. Using comprehensive TME single-cell transcriptome, proteome, and immune cell analysis, we demonstrated that entinostat, a class I HDAC inhibitor, facilitates tumor deposition of the necrosis-targeted immunocytokine NHS-IL12 to promote potent anti-tumor efficacy against established MC38 and CT26 colon carcinoma models, with complete eradication of poorly immunogenic EMT6 breast tumors. Combination therapy reprogrammed the tumor innate and adaptive immunome to an inflamed landscape, where the concerted action of highly functional CD8+ T cells and activated neutrophils drove a dramatic macrophage M1-like polarization leading to complete tumor eradication. A biomarker signature of the mechanism involved in these studies is associated with patients’ overall survival in multiple tumor types. Collectively, these findings provide a rationale for combining NHS-IL12 with entinostat in the clinical setting.
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| Overall design |
Single-cell RNAseq of immune cells in the tumor microenvironment enabled the identification of main immune subsets contributing to innate and adaptive cross-talk
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| Contributor(s) |
Chariou P, Gameiro S, Hicks K, Cam M, Meyer TJ, Bian J, Schlom J |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Mar 31, 2021 |
| Last update date |
Jun 16, 2021 |
| Contact name |
Thomas Joshua Meyer |
| E-mail(s) |
thomas.meyer@nih.gov
|
| Organization name |
National Institutes of Health
|
| Department |
National Cancer Institute
|
| Lab |
CCBR
|
| Street address |
41 Center Drive, Building 41, Room B620
|
| City |
Bethesda |
| State/province |
Maryland |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (1) |
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| Samples (5)
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| Relations |
| BioProject |
PRJNA718881 |
| SRA |
SRP312953 |
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