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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Nov 10, 2023 |
| Title |
Cancer immunotherapy via synergistic co-activation of myeloid cells [RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Myeloid cells coordinate T cell immune evasion in cancer yet are pliable and possess anti-tumor potential. Here, by co-targeting activation molecules we leverage the myeloid compartment as a therapeutic vulnerability in cancer. Myeloid cells in solid tumors expressed activation receptors including the pattern recognition receptor CLEC7A and the TNF receptor superfamily member CD40. In mouse models of checkpoint inhibitor-resistant pancreatic cancer, co-activation of CLEC7A, via systemic β-glucan therapy, and CD40, with agonist antibody treatment, eradicated established tumors and induced immunological memory. Anti-tumor activity was dependent on a cDC1 – T cell axis but did not require classical T cell cytotoxicity or blockade of checkpoint molecules. Rather, targeting CD40 drove T cell-derived IFNγ signaling which converged with CLEC7A activation to program distinct macrophage subsets to facilitate tumor responses. Thus, productive cancer immune surveillance can be invoked by co-activation of complementary myeloid signaling pathways.
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| Overall design |
Comparative gene expression from RNAseq conducted on bulk orthotopic tumors (PDA.7940B mouse tumor cells) untreated or 10 days post-treatment with beta-glucan, anti-CD40 or beta-glucan and anti-CD40
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| Contributor(s) |
Wattenberg MM, Coho H, Herrara VM, Graham K, Stone ML, Xue Y, Chang RB, Cassella C, Liu M, Choi-Bose S, Thomas SK, Choi H, Li Y, Melendez L, Markowitz K, Giannone M, Bose N, Beatty GL |
| Citation(s) |
37976347 |
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| Submission date |
May 18, 2023 |
| Last update date |
Feb 10, 2024 |
| Contact name |
Max M Wattenberg |
| E-mail(s) |
max.wattenberg@pennmedicine.upenn.edu
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| Organization name |
University of Pennsylvania
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| Lab |
Beatty
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| Street address |
3400 Civic Center Blvd
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| City |
Philadelphia |
| State/province |
PENNSYLVANIA |
| ZIP/Postal code |
19104 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (22)
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| This SubSeries is part of SuperSeries: |
| GSE233175 |
Cancer immunotherapy via synergistic co-activation of myeloid cells |
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| Relations |
| BioProject |
PRJNA974099 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE232860_allsamples.deseq.normalized.counts.csv.gz |
1.7 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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