Hahn Andrew W, Gill David M, Pal Sumanta K, Agarwal Neeraj
Department of Internal Medicine, University of Utah, Salt Lake City, UT, 84112 USA.
Department of Oncology, City of Hope Cancer Center, Duarte, CA, 91010 USA.
Immunotherapy. 2017 Jun;9(8):681-692. doi: 10.2217/imt-2017-0024.
The adaptive immune system plays an important role in eradicating malignant cells. Co-stimulatory and co-inhibitory signals to T cells though immune checkpoint receptors are involved in tumorigenesis and metastasis. Exploitation of immune checkpoint inhibitors, PD-1 and CTLA-4, with monoclonal antibodies has created impressive clinical responses. Many other immune checkpoint co-inhibitors and co-stimulators exist, including the B7 superfamily and tumor necrosis factor receptors superfamily. Here, we will examine co-inhibitors and co-stimulators beyond PD-1 and CTLA-4 that are being investigated in active clinical trials. We will review the immunology and preclinical studies that support investigation of these targets. Finally, we will briefly discuss the potential for immunotherapy to be combined with other treatment modalities.
适应性免疫系统在根除恶性细胞方面发挥着重要作用。通过免疫检查点受体传递给T细胞的共刺激和共抑制信号参与肿瘤发生和转移。利用单克隆抗体对免疫检查点抑制剂PD-1和CTLA-4进行治疗已产生了令人瞩目的临床反应。还存在许多其他免疫检查点共抑制因子和共刺激因子，包括B7超家族和肿瘤坏死因子受体超家族。在此，我们将研究除PD-1和CTLA-4之外正在积极临床试验中进行研究的共抑制因子和共刺激因子。我们将回顾支持这些靶点研究的免疫学和临床前研究。最后，我们将简要讨论免疫疗法与其他治疗方式联合使用的潜力。
