Immune checkpoint blockade opens an avenue of cancer immunotherapy with a potent clinical efficacy.
Immune checkpoint blockade opens an avenue of cancer immunotherapy with a potent clinical efficacy.
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DOI：
10.1111/cas.12695
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发表时间：
2015-08
期刊：
影响因子：
5.7
通讯作者：
Tamada K
中科院分区：
文献类型：
--
作者：
Adachi K;Tamada K
肿瘤免疫学的最新进展表明，肿瘤在生长过程中产生免疫抑制环境，使肿瘤能够逃避宿主免疫系统的保护。免疫检查点分子（immune checkpoint molecules）是肿瘤微环境中赋予免疫抑制能力的最重要成分之一，其向免疫活性细胞发出免疫抑制信号。细胞毒性T淋巴细胞相关蛋白4（CTLA-4）和程序性细胞死亡-1（PD-1）是与抗肿瘤免疫抑制密切相关的典型免疫检查点分子。已经开发了针对这些分子的抗体，如伊匹单抗（抗CTLA-4抗体）、纳武单抗和派姆单抗（抗PD-1抗体），并已获得监管机构的批准，并在一些国家使用。用这些抗体治疗证明了先前未观察到的优于常规疗法的临床功效上级。本文首先讨论了肿瘤逃避宿主免疫系统的机制，然后重点介绍了免疫检查点阻断治疗的最新进展以及相关免疫反应的新发现，旨在更好地理解新型癌症免疫治疗。
Recent progress in tumor immunology has revealed that tumors generate immunologically restrained milieu during the process of their growth, which facilitates the escape of tumors from host immune systems. Immune checkpoint molecules, which transduce co-inhibitory signals to immuno-competent cells, are one of the most important components conferring the immunosuppressive capacity in the tumor microenvironment. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death-1 (PD-1) are typical immune checkpoint molecules intimately involved in the suppression of anti-tumor immunity. Antibodies against those molecules have been developed, such as ipilimumab (anti-CTLA-4 antibody), nivolumab and pembrolizumab (anti-PD-1 antibody), and have been approved by regulatory agencies and used in some countries. Treatment with these antibodies demonstrates previously unobserved clinical efficacies superior to the conventional therapies. In this review, we first discuss the escape mechanisms of cancer from host immune systems, and then focus on the recent advances in immune checkpoint blockade therapy and on the new findings of related immune reactions, aiming to provide a better understanding of the novel cancer immunotherapies.