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Updated: Sep 12, 2025
06:35
A Mouse Model to Investigate the Role of Cancer-Associated Fibroblasts in Tumor Growth
Published on: December 22, 2020
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Tumor Cells-Derived FGF-2 Promotes Lymphangiogenesis as a Prognostic Marker in OSCC
Jia Kang1, Aoming Cheng1, Guanzheng Chen1
1Department of Oral and Maxillofacial-Head and Neck Oncology, Beijing Stomatological Hospital, Capital Medical University, Beijing, China.
Summary
Fibroblast growth factor-2 (FGF-2) drives lymphangiogenesis in oral squamous cell carcinoma (OSCC), creating a cold tumor microenvironment. Targeting FGF-2/FGFR1 may improve OSCC prognosis by enhancing CD8+ T cell infiltration.
Area of Science:
- Oncology
- Immunology
- Cancer Biology
Background:
- Oral squamous cell carcinoma (OSCC) is characterized by a "cold" tumor microenvironment, with tumor-associated lymphatic vessels impacting immune cell transport and prognosis.
- The precise role of tumor-induced lymphangiogenesis in CD8+ T cell infiltration and the tumor immune microenvironment of OSCC remains unclear.
Purpose of the Study:
- To investigate the prognostic significance of lymphangiogenesis factors in OSCC.
- To elucidate the effect of fibroblast growth factor-2 (FGF-2) on lymphangiogenesis, CD8+ T cell infiltration, and the tumor microenvironment in OSCC.
Main Methods:
- Analysis of The Cancer Genome Atlas dataset and tissue specimens for prognostic significance of lymphangiogenesis factors, focusing on FGF-2.
- In vivo and in vitro experiments to assess FGF-2's impact on lymphatic endothelial cells and CD8+ T cell infiltration.
- Survival analysis using Kaplan-Meier and log-rank tests; hazard ratio calculated via Cox proportional hazards model.
Main Results:
- High FGF-2 levels and increased peritumoral lymphatic vessels correlate with worse OSCC prognosis.
- Tumor-derived FGF-2 promotes lymphangiogenesis via the FGFR1/PTEN/AKT pathway, increasing CXCL9 secretion to recruit/egress CD8+ T cells.
- FGFR1 inhibition (PD-166866) suppressed lymphangiogenesis and CXCL9, enhancing CD8+ T cell infiltration and inhibiting tumor progression.
Conclusions:
- FGF-2 is a significant prognostic factor in OSCC, inducing lymphangiogenesis and negatively affecting intratumoral CD8+ T cells, thus contributing to a "cold" tumor microenvironment.
- Targeting the FGF-2/FGFR1 pathway presents a potential therapeutic strategy to improve OSCC prognosis by modulating the tumor immune microenvironment.
Keywords:
CD8+ T cellsfibroblast growth factor‐2lymphangiogenesisoral squamous cell carcinomaprognosisMore Related Videos
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