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Human lung carcinomas express Fas ligand
G A Niehans1, T Brunner, S P Frizelle
1Department of Pathology, Minneapolis Veterans Affairs Medical Center and the University of Minnesota Medical School 55417, USA.
Abstract:
To reach a clinically detectable size, neoplasms must be able to suppress or evade a host immune response. Activated T cells may enter apoptosis in the presence of Fas ligand (FasL) (1), and tissue expression of FasL has been shown to contribute to immune privilege in the eye and testis (2, 3). We have demonstrated that all human lung carcinoma cell lines tested (16 of 16) express a Mr 38,000 protein consistent with FasL by immunoblotting, whereas the majority of resected tumors (23 of 28) show positive staining for FasL by immunohistochemistry. DNA sequencing of reverse transcription-PCR products from lung cancer cells and resected lung tumors confirms the presence of human FasL mRNA in these neoplastic tissues. Furthermore, lung carcinoma cells are capable of killing a Fas-sensitive human T cell line (Jurkat) in coculture experiments; this killing was inhibited by a recombinant form of the soluble portion of the Fas receptor (FasFc). FasL expression by neoplastic cells represents a potential mechanism for peripheral deletion of tumor-reactive T-cell clones.
Insights
Human lung carcinoma cells express Fas ligand (FasL), a molecule that can induce T cell death. This suggests FasL may help tumors evade immune detection and grow.
Area of Science:
- Oncology
- Immunology
Background:
- Neoplasms must evade host immune responses to grow.
- Fas ligand (FasL) can induce T cell apoptosis and contributes to immune privilege.
Purpose of the Study:
- To investigate FasL expression in human lung carcinoma.
- To determine if lung carcinoma cells can induce T cell death via FasL.
Main Methods:
- Immunoblotting and immunohistochemistry to detect FasL protein.
- RT-PCR and DNA sequencing to confirm FasL mRNA.
- Co-culture experiments with Jurkat T cells and FasL inhibitors.
Main Results:
- All tested lung carcinoma cell lines (16/16) expressed FasL protein.
- Most resected lung tumors (23/28) stained positive for FasL.
- Lung carcinoma cells induced apoptosis in Jurkat T cells, an effect blocked by FasFc.
Conclusions:
- Lung carcinoma cells express functional FasL.
- FasL expression is a potential mechanism for lung cancer immune evasion through peripheral deletion of tumor-reactive T cells.