Chronic chromosome instability induced by Plk1 results in immune suppression in breast cancer
Chromosome instability (CIN) contributes to resistance to therapies and tumor evolution. Although natural killer (NK) cells can eliminate cells with complex karyotypes, high-CIN human tumors have an immunosuppressive phenotype. To understand which CIN-associated molecular features alter immune recog...
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| Main Authors: | , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
26 December 2023
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| In: |
Cell reports
Year: 2023, Volume: 42, Issue: 12, Pages: 1-22 |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2023.113266 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.celrep.2023.113266 Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S2211124723012780 
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| Author Notes: | Sridhar Kandala, Maria Ramos, Lena Voith von Voithenberg, Alberto Diaz-Jimenez, Sara Chocarro, Johanna Keding, Benedikt Brors, Charles D. Imbusch, and Rocio Sotillo |
| Summary: | Chromosome instability (CIN) contributes to resistance to therapies and tumor evolution. Although natural killer (NK) cells can eliminate cells with complex karyotypes, high-CIN human tumors have an immunosuppressive phenotype. To understand which CIN-associated molecular features alter immune recognition during tumor evolution, we overexpress Polo-like kinase 1 (Plk1) in a Her2+ breast cancer model. These high-CIN tumors activate a senescence-associated secretory phenotype (SASP), upregulate PD-L1 and CD206, and induce non-cell-autonomous nuclear factor κB (NF-κβ) signaling, facilitating immune evasion. Single-cell RNA sequencing from pre-neoplastic mammary glands unveiled the presence of Arg1+ macrophages, NK cells with reduced effector functions, and increased resting regulatory T cell infiltration. We further show that high PLK1-expressing human breast tumors display gene expression patterns associated with SASP, NF-κβ signaling, and immune suppression. These findings underscore the need to understand the immune landscape in CIN tumors to identify more effective therapies, potentially combining immune checkpoint or NF-κβ inhibitors with current treatments. |
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| Item Description: | Gesehen am 25.01.2024 |
| Physical Description: | Online Resource |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2023.113266 |