T cells targeted against a single minor histocompatibility antigen can cure solid tumors
MC Meunier, JS Delisle, J Bergeron, V Rineau… - Nature medicine, 2005 - nature.com
MC Meunier, JS Delisle, J Bergeron, V Rineau, C Baron, C Perreault
Nature medicine, 2005•nature.comT 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)-γ–producing H7a-specific T cells. Intratumoral release of
IFN-γ had two crucial effects: inhibition of tumor angiogenesis and upregulation of major …
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)-γ–producing H7a-specific T cells. Intratumoral release of
IFN-γ had two crucial effects: inhibition of tumor angiogenesis and upregulation of major …
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 H7a minor H antigen can cure established melanomas in mice. Tumor rejection was initiated by preferential extravasation at the tumor site of interferon (IFN)-γ–producing H7a-specific T cells. Intratumoral release of IFN-γ 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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