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Tumour-expressed tissue factor inhibits cellular cytotoxicity
Chao Li1, Lucy M Colman, Mary E W Collier
1Biomedical Section, Department of Biological Sciences, University of Hull, Cottingham Road, HU6 7RX, Hull, UK.
Cancer Immunology, Immunotherapy : CII
|February 3, 2006
Summary
Tissue factor (TF) expressed by tumor cells helps them evade immune attack, promoting survival and metastasis. This immune evasion is primarily mediated by TF's cytoplasmic domain, not its procoagulant function.
Area of Science:
- Oncology
- Immunology
- Cell Biology
Background:
- Tissue factor (TF) expression is linked to increased tumor metastasis.
- The role of TF in protecting disseminated tumor cells from immune surveillance is not fully understood.
Purpose of the Study:
- To investigate if TF expression by tumor cells confers protection against immune recognition and cytotoxicity.
- To elucidate the mechanism by which TF might mediate immune evasion.
Main Methods:
- Engineered HT29 colon carcinoma and K562 lymphoblast cell lines to express a hybrid EGFP-TF protein.
- Developed a novel method using direct measurement of fluorescently labeled target cells to assess cytotoxic activity.
- Utilized peripheral blood mononuclear cells (PBMCs) to challenge tumor cells and measure cytotoxicity.
Main Results:
- Tumor cells expressing TF demonstrated partial evasion of cellular cytotoxicity, with a 15-40% reduction.
- TF's protective effect was largely independent of its procoagulant function.
- A truncated TF form lacking the cytoplasmic domain failed to inhibit cytotoxicity, indicating the domain's crucial role.
Conclusions:
- TF expression in tumor cells promotes immune evasion, enhancing their survival.
- This immune evasion contributes to a higher metastatic rate in tumors expressing TF.
- The cytoplasmic domain of TF is critical for mediating this immune-protective function.