TY  - JOUR
AU  - Kandala, Sridhar
AU  - Ramos, Maria
AU  - Voith von Voithenberg, Lena
AU  - Diaz-Jimenez, Alberto
AU  - Chocarro, Sara
AU  - Keding, Sigrun Johanna Elisabeth
AU  - Brors, Benedikt
AU  - Imbusch, Charles D
AU  - Sotillo, Rocio
TI  - Chronic chromosome instability induced by Plk1 results in immune suppression in breast cancer.
JO  - Cell reports
VL  - 42
IS  - 12
SN  - 2211-1247
CY  - [New York, NY]
PB  - Elsevier
M1  - DKFZ-2023-02372
SP  - 113266
PY  - 2023
N1  - #EA:B220#EA:B330#LA:B220#
AB  - 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.
KW  - CP: Cancer (Other)
KW  - CP: Cell biology (Other)
KW  - Her2(+) breast cancer (Other)
KW  - NF-κβ signaling (Other)
KW  - chromosomal instability (Other)
KW  - immune evasion (Other)
KW  - senescence-associated secretory phenotype, SASP (Other)
KW  - single-cell sequencing (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:37979172
DO  - DOI:10.1016/j.celrep.2023.113266
UR  - https://inrepo02.dkfz.de/record/285438
ER  -