Munhoz Rodrigo Ramella, Postow Michael Andrew
Cancer J. 2018 Jan/Feb;24(1):7-14. doi: 10.1097/PPO.0000000000000299.
The development of new treatment options has dramatically improved the landscape for patients with advanced melanoma. Part of these advances emerged through the identification of the importance of factors that regulate the immune system, including proteins that negatively modulate T cell-mediated responses termed "immune checkpoints." Indeed, blockade of the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) immune checkpoint served as a proof of principle that the manipulation of these molecules could induce robust anticancer effects, yet limited to a small percentage of patients. Targeting a distinct checkpoint, the PD-1 yielded improved outcomes and reduced toxicity compared with CTLA-4 blockade and, in separate studies, chemotherapy. More recently, combined CTLA-4/PD-1 blockade was shown to result in higher response rates, while accompanied by increased toxicity. In this article, we review the clinical development of anti-PD-1 monotherapy and combinations that may expand the benefit of immunotherapy for patients with advanced melanoma.
新治疗方案的发展显著改善了晚期黑色素瘤患者的治疗前景。这些进展部分源于对调节免疫系统的因素重要性的认识，包括对称为“免疫检查点”的负向调节T细胞介导反应的蛋白质的认识。事实上，细胞毒性T淋巴细胞相关抗原4（CTLA-4）免疫检查点的阻断证明了操纵这些分子可诱导强大的抗癌作用，不过仅限于一小部分患者。与CTLA-4阻断以及在单独研究中与化疗相比，靶向另一个不同的检查点——程序性死亡受体1（PD-1）可产生更好的疗效并降低毒性。最近，CTLA-4/PD-1联合阻断显示可带来更高的缓解率，但同时毒性也增加。在本文中，我们回顾了抗PD-1单药治疗以及联合治疗的临床进展，这些治疗可能会扩大免疫疗法对晚期黑色素瘤患者的益处。
