题名：Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity
出处：Nat Med. 2003 May;9(5):562-7.
作者：Curiel TJ, Wei S, Dong H, Alvarez X, Cheng P, Mottram P, Krzysiek R, Knutson K L, Daniel B, Zimmermann MC, David O, Burow M, Gordon A, Dhurandhar N, Myers L, Berggren R, Hemminki A, Alvarez RD, Emilie D, Curiel DT, Chen L, Zou W.
摘要：Suppression of dendritic cell function in cancer patients is thought to contribute to the inhibition of immune responses and disease progression. Molecular mechanisms of this suppression remain elusive, however. Here, we show that a fraction of blood monocyte-derived myeloid dendritic cells (MDCs) express B7-H1, a member of the B7 family, on the cell surface.B7-H1 could be further upregulated by tumor environmental factors. Consistent with this finding, virtually all MDCs isolated from the tissues or draining lymph nodes of ovarian carcinomas express B7-H1. Blockade of B7-H1 enhanced MDC-mediated T-cell activation and was accompanied by downregulation of T-cell interleukin (IL)-10 and upregulation of IL-2 and interferon (IFN)-gamma. T cells conditioned with the B7-H1-blocked MDCs had a more potent ability to inhibit autologous human ovarian carcinoma growth in non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice. Therefore, upregulation of B7-H1 on MDCs in the tumor microenvironment downregulates T-cell immunity. Blockade of B7-H1 represents one approach for cancer immunotherapy.
中文：树突状细胞功能的抑制被认为是癌症病人的免疫抑制及疾病进展的原因之一。然而，这种抑制的分子机制仍不清楚。在此，我们展示了有一部分血单核细胞来源的髓系树突状细胞表达B7H1，树突状细胞表面B7家族的成员之一。肿瘤环境因子能上调B7H1的表达。与这个发现一致，所有的从卵巢癌病人的组织或淋巴液种分离出来的mDC都表达B7-H1 .阻断B7-H1 能加强MDC介导的T细胞活化和降低IL10，上调IL2 和IFNgamma。阻断B7H1的MDC能更好的抑制NODSCID鼠体内人卵巢的生长 。因此，阻断B7-H1 为我们提示了一种治疗癌症的新方法。