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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Sep 19, 2022 |
| Title |
Ferroptosis of tumor-associated neutrophils is immunosuppressive and promotes tumor growth |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Ferroptosis is a non-apoptotic form of regulated cell death triggered by the discoordination of regulatory redox mechanisms culminating in massive peroxidation of polyunsaturated phospholipids. The development of the concept of ferroptosis stemmed from an active search for alternatives to apoptosis in cancer cells. Ferroptosis inducers have shown remarkable effectiveness in killing tumor cells in vitro, yet with no obvious success in experimental animal models, with a notable exception of immune-deficient mice 1,2. This suggests the potential poorly understood contribution of ferroptosis on immune cells. Pathologically activated neutrophils (PMN), termed myeloid-derived suppressor cells (PMN-MDSC), are major negative regulators of anti-tumor immunity3-5. Here, we found that PMN-MDSC in the tumor microenvironment (TME), spontaneously die by ferroptosis. While decreasing the presence of PMN-MDSC, ferroptosis induces the release of oxygenated lipids and limits mouse and human T cell activity. In immune-competent mice, genetic and pharmacological inhibition of ferroptosis abrogates suppressive activity of PMN-MDSC, reduces tumor progression, and synergizes with immune checkpoint blockade (ICB) to suppress the tumor growth. In contrast, induction of ferroptosis in immune-competent mice promotes tumor growth. Thus, ferroptosis is a unique and targetable immunosuppressive mechanism of PMN-MDSC in the TME that can be pharmacologically modulated to limit tumor progression.
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| Overall design |
RNA-seq of granulocytes with Alox15 WT and KO status
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| Contributor(s) |
Gabrilovich D, Kim R |
| Citation(s) |
36385526 |
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| Submission date |
Jun 02, 2022 |
| Last update date |
Dec 09, 2022 |
| Contact name |
Priyankara J Wickramasinghe |
| E-mail(s) |
[email protected]
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| Phone |
2154956837
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| Organization name |
The Wistar Institute
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| Department |
Bioinformatics
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| Lab |
Genomics
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| Street address |
3601 Spruce Street
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| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19104 |
| Country |
USA |
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| Platforms (1) |
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| Samples (7)
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| Relations |
| BioProject |
PRJNA844893 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE205371_Alox15_RNAseq.txt.gz |
328.5 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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