PD-1 blockade in renal cell carcinoma: to equilibrium and beyond.
PD-1 blockade in renal cell carcinoma: to equilibrium and beyond.
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DOI：
10.1158/2326-6066.cir-14-0193
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发表时间：
2014-12
影响因子：
10.1
通讯作者：
Choueiri TK
中科院分区：
文献类型：
--
作者：
Harshman LC;Drake CG;Choueiri TK
在过去的几年里，人们对癌症免疫疗法的兴趣重新抬头。针对抑制性程序性死亡-1（PD-1）通路的阻断抗体的开发代表了实体瘤（如黑色素瘤）治疗的临床突破，这些药物在肾细胞癌（RCC）中显示出巨大的前景。早期的数据令人惊讶，因为它们表明，尽管免疫抑制肿瘤微环境的复杂性已被公认，但阻断单个免疫检查点可以在RCC患者中引起客观反应。重新激活患者自身的免疫细胞以重新激活并靶向肿瘤具有更有选择性地杀死并因此降低毒性的潜在优势。此外，检查点阻断免疫疗法具有诱导记忆反应的优势，这是我们目前的细胞毒性和靶向疗法无法实现的。本Crossroads综述将重点介绍RCC中PD-1阻断的新研究，以及这种T细胞靶向策略如何阻碍肿瘤的逃逸机制，并将免疫系统/肿瘤平衡转移回平衡状态，甚至肿瘤消除。
The past several years have witnessed a resurgence of interest in cancer immunotherapy. The development of blocking antibodies against the inhibitory programmed death-1 (PD-1) pathway represents a clinical break-through in the treatment of solid tumors such as melanoma, and these agents show great promise in renal cell carcinoma (RCC). The early data have been surprising in that they demonstrate that blockade of a single immune checkpoint can elicit objective responses in patients with RCC, despite the recognized complexity of the immunosuppressive tumor microenvironment. Reinvigorating the patient’s own immune cells to reactivate and to target the tumor has the potential advantages of more selective killing and thus decreased toxicity. In addition, checkpoint blockade immunotherapy has the advantage of inducing a memory response that is unattainable with our current cytotoxic and targeted therapies. This Crossroads overview will highlight the emerging investigation of PD-1 blockade in RCC and how this T cell–targeted strategy may thwart the tumor’s escape mechanisms and shift the immune system/tumor balance back to a state of equilibrium and even to tumor elimination.