IFN-γ and Fas ligand are required for graft-versus-tumor activity against renal cell carcinoma in the absence of lethal graft-versus-host disease Journal Article
| Authors: | Ramirez-Montagut, T.; Chow, A.; Kochman, A. A.; Smith, O. M.; Suh, D.; Sindhi, H.; Lu, S.; Borsotti, C.; Grubin, J.; Patel, N.; Terwey, T. H.; Kim, T. D.; Heller, G.; Murphy, G. F.; Liu, C.; Alpdogan, O.; van den Brink, M. R. M. |
| Article Title: | IFN-γ and Fas ligand are required for graft-versus-tumor activity against renal cell carcinoma in the absence of lethal graft-versus-host disease |
| 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-α 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. Copyright © 2007 by The American Association of Immunologists, Inc. |
| Keywords: | controlled study; protein expression; survival rate; genetics; mortality; nonhuman; cd8+ t lymphocyte; cd8-positive t-lymphocytes; animal cell; mouse; animal; cytology; metabolism; mouse mutant; animals; mice; mice, knockout; animal tissue; cell survival; fas antigen; fas ligand; animal experiment; animal model; cell motion; allogenic bone marrow transplantation; cytotoxicity; cell line, tumor; transplantation; mice, inbred balb c; mice, inbred c57bl; kidney carcinoma; physiology; c57bl mouse; biosynthesis; immunology; tumor necrosis factor alpha; bagg albino mouse; gamma interferon; carcinoma, renal cell; tumor necrosis factor related apoptosis inducing ligand; tumor cell line; graft versus host reaction; cell movement; perforin; cytotoxicity, immunologic; fas ligand protein; tumor growth; bone marrow transplantation; graft vs host disease; graft versus leukemia effect; graft vs tumor effect; bioluminescence; graft recipient; cell killing; antigens, cd95; interferon type ii; kidney allograft |
| Journal Title: | Journal of Immunology |
| Volume: | 179 |
| Issue: | 3 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 2007-08-01 |
| Start Page: | 1669 |
| End Page: | 1680 |
| Language: | English |
| PUBMED: | 17641033 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 3" - "Export Date: 17 November 2011" - "CODEN: JOIMA" - "Source: Scopus" |
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