Iron-loaded cancer-associated fibroblasts induce immunosuppression in prostate cancer

Kai Zhang, Kaiyuan Liu, Benxia Hu, Genyu Du, Xinyu Chen, Lingling Xiao, Yingchao Zhang, Luyao Jiang, Na Jing, Chaping Cheng, Jinming Wang, Penghui Xu, You Wang, Pengfei Ma, Guanglei Zhuang, Huifang Zhao, Yujiao Sun, Deng Wang, Qi Wang, Wei Xue, Wei-Qiang Gao, Pengcheng Zhang and Helen He Zhu ()
Additional contact information
Kai Zhang: Shanghai Jiao Tong University School of Medicine
Kaiyuan Liu: Shanghai Jiao Tong University School of Medicine
Benxia Hu: Chinese Academy of Sciences
Genyu Du: Shanghai Jiao Tong University School of Medicine
Xinyu Chen: Shanghai Jiao Tong University School of Medicine
Lingling Xiao: Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine
Yingchao Zhang: Shanghai Jiao Tong University School of Medicine
Luyao Jiang: Shanghai Jiao Tong University School of Medicine
Na Jing: Shanghai Jiao Tong University School of Medicine
Chaping Cheng: Shanghai Jiao Tong University School of Medicine
Jinming Wang: Shanghai Jiao Tong University School of Medicine
Penghui Xu: Shanghai Jiao Tong University School of Medicine
You Wang: Shanghai Jiao Tong University School of Medicine
Pengfei Ma: Shanghai Jiao Tong University School of Medicine
Guanglei Zhuang: Shanghai Jiao Tong University School of Medicine
Huifang Zhao: Shanghai Jiao Tong University School of Medicine
Yujiao Sun: Shanghai Jiao Tong University School of Medicine
Deng Wang: Shanghai Jiao Tong University School of Medicine
Qi Wang: Shanghai Jiao Tong University School of Medicine
Wei Xue: Shanghai Jiao Tong University School of Medicine
Wei-Qiang Gao: Shanghai Jiao Tong University School of Medicine
Pengcheng Zhang: Shanghai Tech University
Helen He Zhu: Shanghai Jiao Tong University School of Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract Iron is an essential biomineral in the human body. Here, we describe a subset of iron-loaded cancer-associated fibroblasts, termed as FerroCAFs, that utilize iron to induce immunosuppression in prostate cancer and predict an unfavorable clinical outcome. FerroCAFs secrete myeloid cell-associated proteins, including CCL2, CSF1 and CXCL1, to recruit immunosuppressive myeloid cells. We report the presence of FerroCAFs in prostate cancer from both mice and human, as well as in human lung and ovarian cancers, and identify a conserved cell surface marker, the poliovirus receptor. Mechanistically, the accumulated iron in FerroCAFs is caused by Hmox1-mediated iron release from heme degradation. The intracellular iron activates the Kdm6b, an iron-dependent epigenetic enzyme, to induce an accessible chromatin state and transcription of myeloid cell-associated protein genes. Targeting the FerroCAFs by inhibiting the Hmox1/iron/Kdm6b signaling axis incurs anti-tumor immunity and tumor suppression. Collectively, we report an iron-loaded FerroCAF cluster that drives immunosuppression through an iron-dependent epigenetic reprogramming mechanism and reveal promising therapeutic targets to boost anti-tumor immunity.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-53233-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53233-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-53233-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().