Journal Article

DKFZ-2023-02372

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Chronic chromosome instability induced by Plk1 results in immune suppression in breast cancer.

Kandala, S. (First author)DKFZ* ; Ramos, M. (First author)DKFZ* ; Voith von Voithenberg, L. (First author)DKFZ* ; Diaz-Jimenez, A.DKFZ* ; Chocarro, S.DKFZ* ; Keding, S. J. E.DKFZ* ; Brors, B.DKFZ* ; Imbusch, C. D.DKFZ* ; Sotillo, R. (Last author)DKFZ*

2023
Elsevier [New York, NY]

This record in other databases:  

Please use a persistent id in citations: doi:10.1016/j.celrep.2023.113266

Abstract: 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.

Keyword(s): CP: Cancer ; CP: Cell biology ; Her2(+) breast cancer ; NF-κβ signaling ; chromosomal instability ; immune evasion ; senescence-associated secretory phenotype, SASP ; single-cell sequencing

Note: #EA:B220#EA:B330#LA:B220#

---

Contributing Institute(s):

1. B220 Molekulare Grundlagen thorakaler Tumoren (B220)
2. Angewandte Bioinformatik (B330)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2023

---

Database coverage:
; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---