Cyclin E1 overexpression triggers interferon signaling and is associated with antitumor immunity in breast cancer

• DOI: 10.1136/jitc-2024-009239
• Publication Date: 2025-03-19T18:01:00Z
• Authors: Shibo Yu; Chantal Stappenbelt; Mengting Chen; Mirte Dekker; Arkajyoti Bhattac...; Tineke van der Sluis; Mieke C Zwager; Carolien P Schröder; Rudolf S N Fehrmann; Marcel A T M van ...; Bert van der Vegt
• Keywords: Cyclin E1; Cyclin D; Cyclin A2

Background Cyclin E1 overexpression drives oncogenesis in several cancers through deregulation of DNA replication and induction genomic instability, which may potentially trigger immune signaling via cytoplasmic DNA. However, the effects cyclin on tumor immunity its response to checkpoint inhibitors remain largely unclear. Methods Tissue microarrays clinical outcomes 398 patients with breast cancer were analyzed explore correlation between expression, patient survival, cell infiltration using immunohistochemistry. Genomic data from publicly available sets three trials evaluating immunotherapy assessed measure impact expression cells microenvironment cancer. In addition, lines inducible employed analyze inflammatory signaling. Results Increased was positively correlated infiltration, including T cells, B natural killer activation interferon-related pathways. Importantly, higher or CCNE1 amplification associated better trials. Mechanistically, resulted micronuclei formation innate signaling, resulting increased migration. Conclusions Our show that associate antitumor warrants investigation into identifying eligible for immunotherapy.