T cells targeted against a single minor histocompatibility antigen can cure solid tumors.

Abstract

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.

• Authors: Marie-Christine Meunier, Jean-Sébastien Delisle, Julie Bergeron, Vincent Rineau, Chantal Baron, Claude Perreault
• Journal: Nature medicine (Nat Med) Vol. 11 Issue 11 Pg. 1222-9 (Nov 2005) ISSN: 1078-8956 [Print] United States
• PMID: 16227989 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Minor Histocompatibility Antigens
• Interferon-gamma

Topics

• Animals
• Cytotoxicity, Immunologic (genetics)
• Female
• Flow Cytometry
• Immunohistochemistry
• Immunotherapy
• Interferon-gamma (biosynthesis)
• Mice
• Mice, Congenic
• Minor Histocompatibility Antigens (immunology)
• Neoplasm Transplantation
• Neoplasms (immunology, therapy)
• Neoplasms, Experimental (therapy)
• T-Lymphocytes (immunology)
• Transplantation, Homologous