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000285438 1001_ $$0P:(DE-He78)d8285822e4aff9a18b05b78084ed3f09$$aKandala, Sridhar$$b0$$eFirst author
000285438 245__ $$aChronic chromosome instability induced by Plk1 results in immune suppression in breast cancer.
000285438 260__ $$a[New York, NY]$$bElsevier$$c2023
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000285438 520__ $$aChromosome instability (CIN) contributes to resistance to therapies and tumor evolution. Although natural killer (NK) cells can eliminate cells with complex karyotypes, high-CIN human tumors have an immunosuppressive phenotype. To understand which CIN-associated molecular features alter immune recognition during tumor evolution, we overexpress Polo-like kinase 1 (Plk1) in a Her2+ breast cancer model. These high-CIN tumors activate a senescence-associated secretory phenotype (SASP), upregulate PD-L1 and CD206, and induce non-cell-autonomous nuclear factor κB (NF-κβ) signaling, facilitating immune evasion. Single-cell RNA sequencing from pre-neoplastic mammary glands unveiled the presence of Arg1+ macrophages, NK cells with reduced effector functions, and increased resting regulatory T cell infiltration. We further show that high PLK1-expressing human breast tumors display gene expression patterns associated with SASP, NF-κβ signaling, and immune suppression. These findings underscore the need to understand the immune landscape in CIN tumors to identify more effective therapies, potentially combining immune checkpoint or NF-κβ inhibitors with current treatments.
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000285438 650_7 $$2Other$$aCP: Cancer
000285438 650_7 $$2Other$$aCP: Cell biology
000285438 650_7 $$2Other$$aHer2(+) breast cancer
000285438 650_7 $$2Other$$aNF-κβ signaling
000285438 650_7 $$2Other$$achromosomal instability
000285438 650_7 $$2Other$$aimmune evasion
000285438 650_7 $$2Other$$asenescence-associated secretory phenotype, SASP
000285438 650_7 $$2Other$$asingle-cell sequencing
000285438 7001_ $$0P:(DE-HGF)0$$aRamos, Maria$$b1$$eFirst author
000285438 7001_ $$0P:(DE-He78)065afb554417f5acd8ea579fc0d13d0b$$aVoith von Voithenberg, Lena$$b2$$eFirst author
000285438 7001_ $$0P:(DE-HGF)0$$aDiaz-Jimenez, Alberto$$b3
000285438 7001_ $$0P:(DE-HGF)0$$aChocarro, Sara$$b4
000285438 7001_ $$0P:(DE-He78)4009b389a34f8d3f41368959e7fd8e6a$$aKeding, Sigrun Johanna Elisabeth$$b5
000285438 7001_ $$0P:(DE-He78)fc949170377b58098e46141d95c72661$$aBrors, Benedikt$$b6
000285438 7001_ $$0P:(DE-HGF)0$$aImbusch, Charles D$$b7
000285438 7001_ $$0P:(DE-HGF)0$$aSotillo, Rocio$$b8$$eLast author
000285438 773__ $$0PERI:(DE-600)2649101-1$$a10.1016/j.celrep.2023.113266$$gVol. 42, no. 12, p. 113266 -$$n12$$p113266$$tCell reports$$v42$$x2211-1247$$y2023
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