%0 Journal Article
%A Kandala, Sridhar
%A Ramos, Maria
%A Voith von Voithenberg, Lena
%A Diaz-Jimenez, Alberto
%A Chocarro, Sara
%A Keding, Sigrun Johanna Elisabeth
%A Brors, Benedikt
%A Imbusch, Charles D
%A Sotillo, Rocio
%T Chronic chromosome instability induced by Plk1 results in immune suppression in breast cancer.
%J Cell reports
%V 42
%N 12
%@ 2211-1247
%C [New York, NY]
%I Elsevier
%M DKFZ-2023-02372
%P 113266
%D 2023
%Z #EA:B220#EA:B330#LA:B220#
%X 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.
%K CP: Cancer (Other)
%K CP: Cell biology (Other)
%K Her2(+) breast cancer (Other)
%K NF-κβ signaling (Other)
%K chromosomal instability (Other)
%K immune evasion (Other)
%K senescence-associated secretory phenotype, SASP (Other)
%K single-cell sequencing (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:37979172
%R 10.1016/j.celrep.2023.113266
%U https://inrepo02.dkfz.de/record/285438