| Accession |
PRJCA022332 |
| Title |
Iron-Loaded Cancer-Associated Fibroblasts Induce Immunosuppression in Prostate Cancer |
| Relevance |
Medical |
| Data types |
Transcriptome or Gene expression
|
| Organisms |
Mus musculus
Mus
|
| Description |
Iron is an essential biomineral in human body. Here, we discover a new subset of ferric iron-loaded cancer-associated fibroblasts (FerroCAFs) that utilizes iron to induce immunosuppression in prostate cancer (PCa) and predicts an unfavorable clinical outcome. FerroCAFs secret myeloid-cell-associated proteins (MASP), including CCL2, CSF1 and CXCL1, to recruit immunosuppressive myeloid cells. Importantly, we demonstrate the existence of FerroCAFs in PCa from both mice and humans, as well as in human lung and ovarian cancers and identify a conserved cell surface marker, the poliovirus receptor (Pvr). Mechanistically, the accumulated iron in FerroCAFs is caused by Heme Oxygenase-1 (Hmox1)-mediated iron release from heme degradation. The intracellular iron activates the lysine demethylase 6B (Kdm6b), an iron-dependent epigenetic enzyme, to trigger an accessible chromatin state and transcription of MASP genes. Targeting the FerroCAFs by inhibiting the Hmox1/iron/Kdm6b signaling axis incurs anti-tumor immunity and significant tumor regression. Collectively, we uncover a novel iron-loaded FerroCAF cluster that drives immunosuppression through an iron-dependent epigenetic reprogramming mechanism and reveal new therapeutic targets to boost anti-tumor immunity. |
| Sample scope |
Single cell |
| Release date |
2024-09-22 |
| Publication |
| PubMed ID |
Article title |
Journal name |
DOI |
Year |
| 39426954
|
Iron-loaded cancer-associated fibroblasts induce immunosuppression in prostate cancer
|
Nature Communications
|
10.1038/s41467-024-53233-1
|
2024
|
|
|
| Grants |
| Agency |
program |
Grant ID |
Grant title |
| National Key R&D Program of China
|
|
2022YFA1302704
|
|
| National Natural Science Foundation of China (NSFC)
|
|
NSFC32022021
|
|
| National Natural Science Foundation of China (NSFC)
|
|
NSFC81972404
|
|
| National Natural Science Foundation of China (NSFC)
|
|
NSFC82372873
|
|
| National Natural Science Foundation of China (NSFC)
|
|
NSFC81872406
|
|
| Shanghai Pilot Program for Basic Research-Shanghai Jiao Tong University
|
|
21TQ1400225
|
|
| Program of Shanghai Academic/Technology Research Leader
|
|
21XD1422300
|
|
| Shanghai Municipal Education Commission Gaofeng Clinical Medicine Grant Support
|
|
20181706
|
|
| Innovative research team of high-level local universities in Shanghai
|
|
N/A
|
|
| 111 project
|
|
B21024
|
|
| Science and Technology Commission of Shanghai Municipality
|
|
20JC1417600
|
|
| Science and Technology Commission of Shanghai Municipality
|
|
21JC1404100
|
|
| Peak Disciplines (Type IV) of Institutions of Higher Learning in Shanghai
|
|
N/A
|
|
| KC Wong foundation
|
|
N/A
|
|
| National project supporting program RJTJ23-ZD-003 of Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine
|
|
RJTJ23ZD003
|
|
|
|
| Submitter |
Helen
He
Zhu (hzhu@shsci.org)
|
| Organization |
Renji Hospital, School of Medicine, Shanghai Jiao Tong University |
| Submission date |
2023-12-23 |
