Fibroblast-Derived TSLP Promotes Ovarian Cancer Metastasis by Altering the Immune Microenvironment

Abstract

Background: Fibroblast-derived Thymic Stromal Lymphopoietin (TSLP), an inflammatory cytokine, plays a significant role in regulating the tumor microenvironment and immune responses. This study aimed to investigate the role of TSLP in ovarian cancer (OVCA) metastasis and its underlying mechanisms that modify the immune microenvironment and drive type 2 immunity. Methods: The role of TSLP in OVCA metastasis was evaluated using both the in vivo and in vitro experimental models. The expression levels of TSLP, its associated immune cell infiltration and type 2 immune-related factors were evaluated in non-metastatic and metastatic OVCA employing flow cytometry, Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR), and Western blot analysis. Results: We found that TSLP was upregulated in fibroblasts and the TSLP receptor (TSLPR) was significantly upregulated in immune cells in the metastatic microenvironment (p < 0.01). Moreover, inhibition of TSLP substantially decreased the migration of both T cells and eosinophils. Furthermore, inhibition of TSLP reduced the formation of metastatic foci and modulated immune response within these foci (p < 0.01). Additionally, both in vivo and in vitro experimental results showed that TSLP promoted OVCA cell migration and invasion, and enhanced type 2 immune response of immune cells (p < 0.01). Conclusion: Our findings indicate that fibroblast-derived TSLP plays a crucial role in promoting OVCA metastasis by altering the immune microenvironment and stimulating type 2 immune response. This study provides a theoretical basis for devising novel therapeutic strategies and targeted treatment of TSLP.