Leader cells promote immunosuppression to drive ovarian cancer progression in vivo
Summary: Over 75% of patients with ovarian cancer present with late-stage disease, often accompanied by extensive metastasis. The metastatic cascade is driven by a sub-population of transcriptionally plastic cells known as ''leader cells'' (LCs), which play a critical role in col...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-11-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724013305 |
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| Summary: | Summary: Over 75% of patients with ovarian cancer present with late-stage disease, often accompanied by extensive metastasis. The metastatic cascade is driven by a sub-population of transcriptionally plastic cells known as ''leader cells'' (LCs), which play a critical role in collective invasion yet remain poorly understood. LCs are marked by the expression of keratin-14 (KRT14), which determines their migratory and invasive capacity in ovarian cancer. This study demonstrates that KRT14+ LCs promote tumor progression through immunosuppression and immune privilege in vivo. In the ID8 syngeneic epithelial ovarian cancer mouse model, tumor-specific loss of KRT14+ LCs impairs tumor progression and metastatic spread without affecting cellular proliferation. Immune profiling shows reduced immunosuppressive regulatory T cells (Tregs) and M2 macrophages and improved CD8+ T cell/Treg ratios in LC knockout (LCKO) mice. Conversely, forced LC overexpression accelerates metastasis and increases the secretion of immunosuppressive chemokines, such as CCL22 and CCL5, highlighting the role of KRT14+ LCs in immune suppression and metastatic progression. |
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| ISSN: | 2211-1247 |