Mitochondrial DNA released by senescent tumor cells enhances PMN-MDSC-driven immunosuppression through the cGAS-STING pathway

Lai, Ping; Liu, Lei; Bancaro, Nicolò; Troiani, Martina; Calì, Bianca; Li, Yuxin; Chen, Jingjing; Singh, Prafull Kumar; Arzola, Rydell Alvarez; Attanasio, Giuseppe; Pernigoni, Nicolò; Pasquini, Emiliano; Mosole, Simone; Rinaldi, Andrea; Sgrignani, Jacopo; Qiu, Shi; Song, Pan; Li, Yingrui; Desbats, María Andrea; Ángel, Azucena Rendón; Mestre, Ricardo Pereira; Cavalli, Andrea; Barile, Lucio; Bono, Johann S. de; Alimonti, Andrea

doi:10.1016/j.immuni.2025.03.005

articleImmunityApr 1, 2025HYBRID OA

Mitochondrial DNA released by senescent tumor cells enhances PMN-MDSC-driven immunosuppression through the cGAS-STING pathway

PLPing Lai LLLei Liu NBNicolò Bancaro MTMartina Troiani BCBianca Calì

Università della Svizzera italiana · Institute of Oncology Research · +7 more institutions

PubMed

Indexed incrossrefpubmed

Abstract

Mitochondrial dysfunction is a hallmark of cellular senescence. Here, we investigated whether senescent cells release mitochondrial (mt)DNA into the extracellular space and its impact on innate immunity. We found that both primary senescent cells and tumor cells undergoing therapy-induced senescence actively released mtDNA into the extracellular environment. mtDNA released by senescent cells was packaged within extracellular vesicles and selectively transferred to polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in the tumor microenvironment. Upon uptake, extracellular mtDNA enhanced the immunosuppressive activity of PMN-MDSCs via cGAS-STING-NF-κB signaling, thereby promoting tumor progression.…

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95

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FWCI: 57.16
Percentile: 100%
References: 66

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Topics & keywords

Topics

Keywords

Immunosuppression
Biology
Sting
Mitochondrial DNA
Cancer research
Mitochondrion
Immunology
Virology

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