Introduction to checkpoint inhibitors and cancer immunotherapy.
Introduction to checkpoint inhibitors and cancer immunotherapy.
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DOI：
10.1111/imr.12531
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发表时间：
2017-03
影响因子：
8.7
通讯作者：
Sharpe AH
中科院分区：
文献类型：
--
作者：
Sharpe AH
免疫反应由一个精致的制衡系统调节，使有效的保护性免疫和耐受性成为可能。许多免疫检查点控制先天性和适应性免疫系统的细胞，决定其功能。刺激性检查点途径促进幼稚T细胞的激活，以及效应、记忆和调节性T细胞反应。抑制性检查点途径限制T细胞活化的阈值和免疫应答的持续时间，并且具有调节炎症、耐受性和稳态的消退的多种作用。肿瘤已经劫持了抑制检查点以逃避免疫根除。T细胞检查点抑制剂CTLA-4和PD-1的阻断已显示出显著持久的临床应答，但仅在一部分患者中有效[1-5]。联合治疗方法进一步提高了缓解率[6]。这些成功激发了人们对确定先天和适应性检查点在控制免疫抑制肿瘤微环境中的作用以及开发针对这些检查点进行癌症免疫治疗的策略的极大兴趣。
Immune responses are regulated by an exquisite system of checks and balances that enable effective protective immunity and tolerance. A number of immunological checkpoints control cells of the innate and adaptive immune system that determine their function. Stimulatory checkpoint pathways promote activation of naïve T cells, as well as effector, memory and regulatory T cell responses. Inhibitory checkpoint pathways limit the threshold for T cell activation and duration of immune responses, and have diverse effects that regulate resolution of inflammation, tolerance and homeostasis. Tumors have hijacked inhibitory checkpoints to evade immune eradication. Blockade of the T cell checkpoint inhibitors CTLA-4 and PD-1 has shown remarkably durable clinical responses, but is effective in only a subset of patients [1-5]. Combination therapy approaches are further improving response rates [6]. These successes have stimulated great interest in determining the roles of innate and adaptive checkpoints in controlling the immunosuppressive tumor microenvironment, and developing strategies to target these checkpoints for cancer immunotherapy.