T cells targeted against a single minor histocompatibility antigen can cure solid tumors.
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.
Meunier
Marie-Christine
MC
Institute of Research in Immunology and Cancer, University of Montreal, C.P. 6128, Downtown Station, Montreal, Quebec, Canada, H3C 3J7.
Delisle
Jean-Sébastien
JS
Bergeron
Julie
J
Rineau
Vincent
V
Baron
Chantal
C
Perreault
Claude
C
D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007167:Immunotherapy; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D020297:Mice, Congenic; D015778:Minor Histocompatibility Antigens / Q000276:immunology*; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D009374:Neoplasms, Experimental / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous
D015778:Minor Histocompatibility Antigens; D007371:Interferon-gamma