Meunier Marie-Christine, Delisle Jean-Sébastien, Bergeron Julie, Rineau Vincent, Baron Chantal, Perreault Claude
Institute of Research in Immunology and Cancer, University of Montreal, C.P. 6128, Downtown Station, Montreal, Quebec, Canada, H3C 3J7.
Nat Med. 2005 Nov;11(11):1222-9. doi: 10.1038/nm1311. Epub 2005 Oct 16.
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.
对次要组织相容性（H）抗原产生反应的T细胞在治疗白血病方面极为有效，但它们能否根除实体瘤仍不清楚。我们报告称，注射针对免疫显性H7（a）次要H抗原致敏的CD8（+）T细胞可以治愈小鼠体内已形成的黑色素瘤。肿瘤排斥反应是由产生干扰素（IFN）-γ的H7（a）特异性T细胞在肿瘤部位优先渗出引发的。肿瘤内IFN-γ的释放有两个关键作用：抑制肿瘤血管生成和上调肿瘤细胞上主要组织相容性复合体（MHC）I类分子的表达。尽管H7（a）广泛表达，但少数H7（a）特异性T细胞在淋巴外器官中的扩散既未引起移植物抗宿主病（GVHD），也未导致白癜风，因为宿主非造血细胞因其低水平的MHC I类分子表达而受到保护。我们的临床前模型为基于次要H抗原的免疫疗法如何用于治疗人类实体瘤提供了独特的见解。
