The DOI matches its Crossref record; 67 of the 67 references it cites were found in a registry or an index.
Mitochondrial DNA released by senescent tumor cells enhances PMN-MDSC-driven immunosuppression through the cGAS-STING pathway
Open accessAbstract
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. While STING activation directly induced NF-κB signaling, it also activated PKR-like endoplasmic reticulum kinase (PERK), which further amplified NF-κB activity, in PMN-MDSCs. mtDNA release from senescent cells was mediated by voltage-dependent anion channels (VDACs), and pharmacological inhibition of VDAC reduced extracellular mtDNA levels, reversed PMN-MDSC-driven immunosuppression, and enhanced chemotherapy efficacy in prostate cancer mouse models. These findings suggest that targeting mtDNA release could reprogram the immunosuppressive tumor microenvironment, improving therapeutic outcomes for chemotherapy-treated patients.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“It can recognize mtDNA released during liver injury, leading to its activation and the triggering of inflammation with the production of type I interferons (IFNs) and proinflammatory cytokines, which exacerbates liver inflammation and hepatocyte damage (20–22).”
From Matrix mechanical remodeled carrier-free nanosystem for programmable closed-loop reversal of liver fibrosis via STING alkylation (2025) · cites this paper as [20]
Citations
Cites
STAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709
The senescence-associated secretory phenotype: the dark side of tumor suppression
Coppé, J.-P., Desprez, P.-Y., Krtolica, A., & Campisi, J. (2010) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-121808-102144 · Cited by 5,206
Circulating mitochondrial DAMPs cause inflammatory responses to injury
Zhang, Q., Raoof, M., Chen, Y., Sumi, Y., Sursal, T., Junger, W., Brohi, K., Itagaki, K., & Hauser, C. J. (2010) · Nature · doi:10.1038/nature08780 · Cited by 3,812
Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards
Bronte, V., Brandau, S., Chen, S.-H., Colombo, M. P., Frey, A. B., Greten, T. F., Mandruzzato, S., Murray, P. J., Ochoa, A., Ostrand-Rosenberg, S., et al. (2016) · Nature Communications · doi:10.1038/ncomms12150 · Cited by 2,751
Hallmarks of Cellular Senescence
Hernandez-Segura, A., Nehme, J., & Demaria, M. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.02.001 · Cited by 2,605
Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis
Chen, Z., Trotman, L. C., Shaffer, D., Lin, H.-K., Dotan, Z. A., Niki, M., Koutcher, J. A., Scher, H. I., Ludwig, T., Gerald, W., et al. (2005) · Nature · doi:10.1038/nature03918 · Cited by 1,993
Mitochondrial DNA stress primes the antiviral innate immune response
West, A. P., Khoury-Hanold, W., Staron, M., Tal, M. C., Pineda, C. M., Lang, S. M., Bestwick, M., Duguay, B. A., Raimundo, N., MacDuff, D. A., et al. (2015) · Nature · doi:10.1038/nature14156 · Cited by 1,975
Myeloid-derived suppressor cells in the era of increasing myeloid cell diversity
Veglia, F., Sanseviero, E., & Gabrilovich, D. I. (2021) · Nature Reviews Immunology · doi:10.1038/s41577-020-00490-y · Cited by 1,940
Krtolica, A., Parrinello, S., Lockett, S., Desprez, P.-Y., & Campisi, J. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.211053698 · Cited by 1,730
DAMP-sensing receptors in sterile inflammation and inflammatory diseases
Gong, T., Liu, L., Jiang, W., & Zhou, R. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-019-0215-7 · Cited by 1,672
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Bai, X., Guo, Y.-R., Zhao, Z., Li, X., Dai, D.-Q., Zhang, J., Li, Y.-S., & Zhang, C. (2025) · Cancer Letters · doi:10.1016/j.canlet.2025.217772 · Cited by 140
Self-citationColucci, M., Sarill, M., Maddalena, M., Valdata, A., Troiani, M., Massarotti, M., Bolis, M., Bressan, S., Kohl, A., Robesti, D., et al. (2025) · Cancer Cell · doi:10.1016/j.ccell.2025.05.015 · Cited by 143
Self-citationLi, H., Cai, R., Zhou, Y., Jiang, Y., & Tan, S. (2025) · Journal of Neuroinflammation · doi:10.1186/s12974-025-03563-8 · Cited by 72
Cellular senescence in cancer: from mechanism paradoxes to precision therapeutics
Feng, T., Xie, F., Lee, L. M.-Y., Lin, Z., Tu, Y., Lyu, Y., Yu, P., Wu, J., Chen, B., Zhang, G., et al. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02419-2 · Cited by 70
The cGAS-STING pathway: a dual regulator of immune response in cancer and therapeutic implications
Huang, Z., Zhu, J., Zhou, Y. L., & Shi, J. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-025-06843-2 · Cited by 60
Metadata
- Authors
- Lai, P., Liu, L., Bancaro, N., Troiani, M., Calì, B., Li, Y., Chen, J., Singh, P. K., Arzola, R. A., Attanasio, G., Pernigoni, N., Pasquini, E., Mosole, S., Rinaldi, A., Sgrignani, J., Qiu, S., Song, P., Li, Y., Desbats, M. A., Ángel, A. R., Mestre, R. P., Cavalli, A., Barile, L., de Bono, J., & Alimonti, A.
- Affiliations
- Institute of Oncology Research (CH)
- Institute for Research in Biomedicine (CH)
- West China Hospital of Sichuan University (CN)
- Ente Ospedaliero Cantonale (CH)
- Istituto Cardiocentro Ticino (CH)
- University of Padua (IT)
- Corresponding author
- Alimonti, Andrea
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2025-04
- Volume
- 58
- Issue
- 4
- Pages
- 811-825.e7
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W4409254393
- Cited by
- 174
- References
- 65
- Citations by year
- 2026: 139 · 2025: 35
- FWCI
- 64.42
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Immunity (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Repository for Publications and Research Data (ETH Zurich) (publishedVersion, cc-by-nc)
- IRIS (submittedVersion)
- Padua Research Archive (University of Padova) (submittedVersion, cc-by-nc-nd)
- ETH Zürich Research Collection
- Funders
- European Research Council (CoG 683136)
- Cancer Research Foundation Switzerland (KFS-5262-02-2021, KFS-4267-08-2017, RWP-4813-06-2019)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (201274, 176045, 202302, 216062)
- Fondazione AIRC per la ricerca sul cancro ETS (IG 22030)
- ISREC Foundation
- Prostate Cancer Foundation (19CHAL08)
- Novartis Foundation for Medical-Biological Research (21A009)
- Associazione Italiana per la Ricerca sul Cancro
- Portland Community Fund
- Novartis Foundation
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- mitochondrial DNA release, cellular senescence, therapy-induced senescence, polymorphonuclear myeloid-derived suppressor cells, cGAS-STING pathway, NF-κB signaling, PERK signaling, extracellular vesicles, voltage-dependent anion channel, tumor immunosuppression, tumor microenvironment, prostate cancer, chemotherapy efficacy, innate immunity
- MeSH terms
- Myeloid-Derived Suppressor Cells, STING Protein, Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase, Animals, DNA, Mitochondrial, Humans, Immune Tolerance, Male, Membrane Proteins, Mice, Inbred C57BL, Mitochondria, Neutrophils, Nucleotidyltransferases, Prostatic Neoplasms, Signal Transduction, NF-kappa B, Cellular Senescence, Cell Line, Tumor, Mice, Tumor Microenvironment
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
