Dong Haidong, Strome Scott E, Salomao Diva R, Tamura Hideto, Hirano Fumiya, Flies Dallas B, Roche Patrick C, Lu Jun, Zhu Gefeng, Tamada Koji, Lennon Vanda A, Celis Esteban, Chen Lieping
Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA.
Nat Med. 2002 Aug;8(8):793-800. doi: 10.1038/nm730. Epub 2002 Jun 24.
B7-H1, a recently described member of the B7 family of costimulatory molecules, is thought to be involved in the regulation of cellular and humoral immune responses through the PD-1 receptor on activated T and B cells. We report here that, except for cells of the macrophage lineage, normal human tissues do not express B7-H1. In contrast, B7-H1 is abundant in human carcinomas of lung, ovary and colon and in melanomas. The pro-inflammatory cytokine interferon-gamma upregulates B7-H1 on the surface of tumor cell lines. Cancer cell-associated B7-H1 increases apoptosis of antigen-specific human T-cell clones in vitro, and the apoptotic effect of B7-H1 is mediated largely by one or more receptors other than PD-1. In addition, expression of B7-H1 on mouse P815 tumor increases apoptosis of activated tumor-reactive T cells and promotes the growth of highly immunogenic B7-1(+) tumors in vivo. These findings have implications for the design of T cell-based cancer immunotherapy.
B7-H1是共刺激分子B7家族中最近被描述的一个成员，被认为通过活化的T细胞和B细胞上的PD-1受体参与细胞免疫和体液免疫反应的调节。我们在此报告，除巨噬细胞系细胞外，正常人体组织不表达B7-H1。相反，B7-H1在人肺癌、卵巢癌和结肠癌以及黑色素瘤中大量存在。促炎细胞因子干扰素-γ上调肿瘤细胞系表面的B7-H1。癌细胞相关的B7-H1在体外增加抗原特异性人T细胞克隆的凋亡，且B7-H1的凋亡作用主要由PD-1以外的一种或多种受体介导。此外，小鼠P815肿瘤上B7-H1的表达增加活化的肿瘤反应性T细胞的凋亡，并在体内促进高免疫原性B7-1(+)肿瘤的生长。这些发现对基于T细胞的癌症免疫治疗设计具有启示意义。
