Nature Medicine 11, 1222 - 1229 (2005)
Published online: 16 October 2005; | doi:10.1038/nm1311
T cells targeted against a single minor histocompatibility antigen can cure solid tumorsMarie-Christine Meunier1, 2, Jean-Sébastien Delisle1, 2, Julie Bergeron2, Vincent Rineau1, 2, Chantal Baron1, 2
& Claude Perreault1, 21
Institute of Research in Immunology and Cancer, University of Montreal, C.P. 6128, Downtown Station, Montreal, Quebec, Canada, H3C 3J7. 2
Guy-Bernier Research Center, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada H1T 2M4.
Correspondence should be addressed to Claude Perreault c.perreault@videotron.ca 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 H7a minor H antigen can cure established melanomas in mice. Tumor rejection was initiated by preferential extravasation at the tumor site of interferon (IFN)- –producing H7a-specific T cells. Intratumoral release of IFN- 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 H7a, dissemination of a few H7a-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.
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