Leader cells promote immunosuppression to drive ovarian cancer progression in vivo

• DOI: 10.1016/j.celrep.2024.114979
• Publication Date: 2024-11-13T21:04:23Z
• Authors: Amy L. Wilson; Laura R. Moffitt; Brittany R. Doran; Bashirah Basri; Jennie Do; Thomas W. Jobling; Magdalena Plebanski; Andrew N. Stephens; Maree Bilandzic
• Keywords: Immunosuppression

Over 75% of patients with ovarian cancer present late-stage disease, often accompanied by extensive metastasis. The metastatic cascade is driven a sub-population transcriptionally plastic cells known as "leader cells" (LCs), which play critical role in collective invasion yet remain poorly understood. LCs are marked the expression keratin-14 (KRT14), determines their migratory and invasive capacity cancer. This study demonstrates that KRT14+ promote tumor progression through immunosuppression immune privilege vivo. In ID8 syngeneic epithelial mouse model, tumor-specific loss impairs spread without affecting cellular proliferation. Immune profiling shows reduced immunosuppressive regulatory T (Tregs) M2 macrophages improved CD8