Mechanisms of Resistance to PD-1 and PD-L1 Blockade.
Mechanisms of Resistance to PD-1 and PD-L1 Blockade.
复制标题
对PD-1和PD-L1阻滞的抗性机制。
DOI：
10.1097/ppo.0000000000000303
复制
发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Ribas A
中科院分区：
文献类型：
--
作者：
Nowicki TS;Hu-Lieskovan S;Ribas A
通过阻断PD-1/PD-L1检查点的癌症免疫疗法彻底改变了多种恶性肿瘤的治疗方法，产生了传统细胞毒性抗癌药所不具备的持久治疗效果。然而，这些疗法在相当大比例的患者中无效，一些最初的应答者最终对这些复发疾病的疗法产生抵抗力。导致对PD-1/PD-L1抑制的原发和获得性耐药的机制是不同的，在单个患者中可能是多因素的和重叠的。随着对PD-1/PD-L1阻滞剂耐药机制的进一步研究，正在开发新的策略来预防或逆转对治疗的耐药性，从而改善患者的预后。
Cancer immunotherapy utilizing blockade of the PD-1/PD-L1 checkpoint has revolutionized the treatment of a wide variety of malignancies, leading to durable therapeutic responses not typically seen with traditional cytotoxic anti-cancer agents. However, these therapies are ineffective in a significant percentage of patients, and some initial responders eventually develop resistance to these therapies with relapsed disease. The mechanisms leading to both primary and acquired resistance to PD-1/PD-L1 inhibition are varied, and can be both multifactorial and overlapping in an individual patient. As the mechanisms of resistance to PD-1/PD-L1 blockade continue to be further characterized, new strategies are being developed to prevent or reverse resistance to therapy, leading to improved patient outcomes.