University of Pittsburgh School of Medicine, PA, Pittsburgh, USA.
Immunotherapy. 2009 Mar;1(2):249-64. doi: 10.2217/1750743X.1.2.249.
While immunotherapy for cancer has become increasingly popular, clinical benefits for such approaches remain limited. This is likely due to tumor-associated immune suppression, particularly in the advanced-disease setting. Thus, a major goal of novel immunotherapeutic design has become the coordinate reversal of existing immune dysfunction and promotion of specific tumoricidal T-cell function. Costimulatory members of the TNF-receptor family are important regulators of T-cell-mediated immunity. Notably, agonist ligation of these receptors restores potent antitumor immunity in the tumor-bearing host. Current Phase I/II evaluation of TNF-receptor agonists as single-modality therapies will illuminate their safety, mechanism(s) of action, and best use in prospective combinational immunotherapy approaches capable of yielding superior benefits to cancer patients.
虽然癌症的免疫疗法越来越受欢迎，但此类方法的临床益处仍然有限。这可能是由于肿瘤相关的免疫抑制，尤其是在晚期疾病中。因此，新型免疫治疗设计的主要目标已经成为协调逆转现有的免疫功能障碍和促进特异性杀瘤 T 细胞功能。TNF 受体家族的共刺激成员是 T 细胞介导免疫的重要调节剂。值得注意的是，这些受体的激动剂交联可恢复荷瘤宿主中强大的抗肿瘤免疫。目前正在进行 TNF 受体激动剂作为单一治疗模式的 I/II 期评估，这将阐明它们的安全性、作用机制以及在有希望为癌症患者带来更好获益的前瞻性联合免疫治疗方法中的最佳应用。
