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Single-cell transcriptomics reveals ferrimagnetic vortex iron oxide nanoring-mediated mild magnetic hyperthermia exerts antitumor effects by alleviating macrophage suppression in breast cancer - 05/01/24

Doi : 10.1016/j.biopha.2023.115954 
Pei Xi a, c, Shihui Liu a, Jiaxuan Tang a, Xun Wang a, Yongkang Liu a, Xinxin Wang a, Shuwei Hu a, Kaixuan Wang a, Wang Li a, Zhiye Cai a, Hailong Shi b, ⁎ , Penggao Dai a, c, ⁎
a National Engineering Research Center for Miniaturized Detection Systems, College of Life Science, Northwest University of Xi’an, 710069 Shaanxi, China 
b School of Basic Medicine, Shaanxi University of Chinese Medicine, Xi’an-Xianyang New Economic Zone, 712046 Shaanxi, China 
c Shaanxi Lifegen Co., Ltd., Xi’ an, China 

⁎ Correspondence to: School of Basic Medicine, Shaanxi University of Chinese Medicine, Xixian New Area 712046, Shaanxi, China. School of Basic Medicine, Shaanxi University of Chinese Medicine Xixian New Area Shaanxi 712046 China ⁎⁎ Correspondence to: National Engineering Research Center for Miniaturized Detection Systems, College of Life Science, Northwest University, No.229, North Taibai Road, Beilin District, Xi’an 710069, Shaanxi Province, China. National Engineering Research Center for Miniaturized Detection Systems, College of Life Science, Northwest University No.229, North Taibai Road, Beilin District Xi’an Shaanxi Province 710069 China

Abstract

The potential of Ferrimagnetic vortex iron oxide nanoring-mediated mild magnetic hyperthermia (FVIO-MHT) in solid tumor therapy has been demonstrated. However, the impact of FVIO-MHT on the tumor microenvironment (TME) remains unclear. This study utilized single-cell transcriptome sequencing to examine the alterations in the TME in response to FVIO-MHT in breast cancer. The results revealed the cellular composition within the tumor microenvironment (TME) was primarily modified due to a decrease in tumor cells and an increased infiltration of myeloid cells. Subsequently, an enhancement in active oxygen (ROS) metabolism was observed, indicating oxidative damage to tumor cells. Interestingly, FVIO-MHT reprogrammed the macrophages’ phenotypes, as evidenced by alterations in the transcriptome characteristics associated with both classic and alternative activated phenotypes. And an elevated level of ROS generation and oxidative phosphorylation suggested that activated phagocytosis and inflammation occurred in macrophages. Additionally, cell–cell communication analysis revealed that FVIO-MHT attenuated the suppression between tumor cells and macrophages by inhibiting phagocytic checkpoint and macrophage migration inhibitory factor signaling pathways. Inhibition of B2m , an anti-phagocytosis checkpoint, could promote macrophage-mediated phagocytosis and significantly inhibit tumor growth. These data emphasize FVIO-MHT may promote the antitumor capabilities of macrophages by alleviating the suppression between tumor cells and macrophages.

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Graphical Abstract




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El texto completo de este artículo está disponible en PDF.

Highlights

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Single-cell transcriptome reveals the microenvironment after magnetic hyperthermia.
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The interaction between tumor cells and macrophages was inhibited.
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Insufficient B2m enhances macrophage-mediated phagocytosis to block tumor growth.
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Magnetic hyperthermia promotes granulocyte response to inflammation.

El texto completo de este artículo está disponible en PDF.

Abbreviations : FIVO-MHT, MNPs, MNP-NT, AMF, SPIONs, scRNA-seq, TME, TAMs, DC, TIL, Inf. M φ , Res. M φ , OGCs, OXPHS, GSEA, IHC, ΔB2m, WT, DAMP

Keywords : Ferrimagnetic vortex-domain iron oxide nanoring, Mild magnetic hyperthermia, Single-cell RNA sequencing, Tumor microenvironment, Macrophages, Phagocytosis checkpoints


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© 2023  The Authors. Publicado por Elsevier Masson SAS. Todos los derechos reservados.
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