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

KIZ OpenIR

	Iron-loaded cancer-associated fibroblasts induce immunosuppression in prostate cancer
	Zhang, K; Liu, KY; Hu, BX; Du, GY; Chen, XY; Xiao, LL; Zhang, YC; Jiang, LY; Jing, N; Cheng, CP; Wang, JM; Xu, PH; Wang, Y; Ma, PF; Zhuang, GL; Zhao, HF; Sun, YJ; Wang, D; Wang, Q; Xue, W; Gao, WQ; Zhang, PC; Zhu, HH
	2024
发表期刊	NAT COMMUN
卷号	15 期号:1
摘要	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. Prostate cancers (PCa) are characterized by an immunosuppressive tumor microenvironment. Here the authors identify a subset of iron-loaded cancer-associated fibroblasts secreting myeloid cell-associated proteins and driving immunosuppression in PCa.
收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14706
专题	昆明动物研究所
推荐引用方式 GB/T 7714	Zhang, K,Liu, KY,Hu, BX,et al. Iron-loaded cancer-associated fibroblasts induce immunosuppression in prostate cancer[J]. NAT COMMUN,2024,15(1).
APA	Zhang, K.,Liu, KY.,Hu, BX.,Du, GY.,Chen, XY.,...&Zhu, HH.(2024).Iron-loaded cancer-associated fibroblasts induce immunosuppression in prostate cancer.NAT COMMUN,15(1).
MLA	Zhang, K,et al."Iron-loaded cancer-associated fibroblasts induce immunosuppression in prostate cancer".NAT COMMUN 15.1(2024).

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QT2025041021.pdf（8603KB）	期刊论文	出版稿	开放获取	CC BY-NC-SA	请求全文