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IFN-gamma and Fas ligand are required for graft-versus-tumor activity against renal cell carcinoma in the absence of lethal graft-versus-host disease
- Source :
- Journal of immunology (Baltimore, Md. : 1950). 179(3)
- Publication Year :
- 2007
-
Abstract
- To determine the mechanisms of graft-versus-tumor (GVT) activity in the absence of graft-versus-host disease (GVHD) against a solid tumor, we established two allogeneic bone marrow transplantation models with a murine renal cell carcinoma (RENCA). The addition of 0.3 × 106 donor CD8+ T cells to the allograft increased the survival of tumor-bearing mice without causing GVHD. The analysis of CD8+ T cells deficient in cytotoxic molecules demonstrated that anti-RENCA activity is dependent on IFN-γ and Fas ligand (FasL), but does not require soluble or membrane-bound TNF-α, perforin, or TRAIL. Recipients of IFN-γ−/− CD8+ T cells are unable to reject RENCA compared with recipients of wild-type CD8+ T cells and, importantly, neither group develops severe GVHD. IFN-γ−/− CD8+ T cells derived from transplanted mice are less able to kill RENCA cells in vitro, while pretreatment of RENCA cells with IFN-γ enhances class I and FasL expression and rescues the lytic capacity of IFN-γ−/− CD8+ T cells. These results demonstrate that the addition of low numbers of selected donor CD8+ T cells to the allograft can mediate GVT activity without lethal GVHD against murine renal cell carcinoma, and this GVT activity is dependent on IFN-γ and FasL.
- Subjects :
- Cytotoxicity, Immunologic
Fas Ligand Protein
Immunology
Graft vs Host Disease
CD8-Positive T-Lymphocytes
Fas ligand
Interleukin 21
Interferon-gamma
Mice
Cell Movement
Cell Line, Tumor
medicine
Immunology and Allergy
Cytotoxic T cell
Animals
fas Receptor
Carcinoma, Renal Cell
Bone Marrow Transplantation
Mice, Knockout
Mice, Inbred BALB C
biology
Graft vs Tumor Effect
medicine.disease
In vitro
Mice, Inbred C57BL
surgical procedures, operative
Graft-versus-host disease
Perforin
Lytic cycle
Cancer research
biology.protein
Female
CD8
Subjects
Details
- ISSN :
- 00221767
- Volume :
- 179
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Accession number :
- edsair.doi.dedup.....a80366841a4bb71dc497e47db4811bad