T cells targeted against a single minor histocompatibility antigen can cure solid tumors
| Autor: | Vincent Rineau, Jean-Sébastien Delisle, Julie Bergeron, Marie-Christine Meunier, Chantal Baron, Claude Perreault |
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| Rok vydání: | 2005 |
| Předmět: |
Cytotoxicity
Immunologic T-Lymphocytes CD1 Major histocompatibility complex General Biochemistry Genetics and Molecular Biology Minor Histocompatibility Antigens Interferon-gamma Mice Mice Congenic Antigen Neoplasms MHC class I Minor histocompatibility antigen Animals Transplantation Homologous Cytotoxic T cell Antigen-presenting cell biology Neoplasms Experimental General Medicine Flow Cytometry Immunohistochemistry Immunology biology.protein Female Immunotherapy Neoplasm Transplantation CD8 |
| Zdroj: | Nature Medicine. 11:1222-1229 |
| ISSN: | 1546-170X 1078-8956 |
| DOI: | 10.1038/nm1311 |
| Popis: | T cells responsive to minor histocompatibility (H) antigens are extremely effective in curing leukemia but it remains unknown whether they can eradicate solid tumors. We report that injection of CD8(+) T cells primed against the immunodominant H7(a) minor H antigen can cure established melanomas in mice. Tumor rejection was initiated by preferential extravasation at the tumor site of interferon (IFN)-gamma-producing H7(a)-specific T cells. Intratumoral release of IFN-gamma had two crucial effects: inhibition of tumor angiogenesis and upregulation of major histocompatibility complex (MHC) class I expression on tumor cells. Despite ubiquitous expression of H7(a), dissemination of a few H7(a)-specific T cells in extralymphoid organs caused neither graft-versus-host disease (GVHD) nor vitiligo because host nonhematopoietic cells were protected by their low expression of MHC class I. Our preclinical model yields unique insights into how minor H antigen-based immunotherapy could be used to treat human solid tumors. |
| Databáze: | OpenAIRE |
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