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Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance
Annual Review of Pathology: Mechanisms of Disease ( IF 36.2 ) Pub Date : 2021-01-26 , DOI: 10.1146/annurev-pathol-042020-042741
Sreya Bagchi 1 , Robert Yuan 1 , Edgar G. Engleman 1
Affiliation  

Immune checkpoint inhibitors (ICIs) have made an indelible mark in the field of cancer immunotherapy. Starting with the approval of anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA-4) for advanced-stage melanoma in 2011, ICIs—which now also include antibodies against programmed cell death 1 (PD-1) and its ligand (PD-L1)—quickly gained US Food and Drug Administration approval for the treatment of a wide array of cancer types, demonstrating unprecedented extension of patient survival. However, despite the success of ICIs, resistance to these agents restricts the number of patients able to achieve durable responses, and immune-related adverse events complicate treatment. Thus, a better understanding of the requirements for an effective and safe antitumor immune response following ICI therapy is needed. Studies of both tumoral and systemic changes in the immune system following ICI therapy have yielded insight into the basis for both efficacy and resistance. Ultimately, by building on these insights, researchers should be able to combine ICIs with other agents, or design new immunotherapies, to achieve broader and more durable efficacy as well as greater safety. Here, we review the history and clinical utility of ICIs, the mechanisms of resistance to therapy, and local and systemic immune cell changes associated with outcome.

中文翻译:


免疫检查点抑制剂治疗癌症:临床影响及反应和耐药机制

免疫检查点抑制剂(ICIs)在癌症免疫治疗领域已树立了不可磨灭的烙印。从2011年批准用于晚期黑素瘤的抗细胞毒性T淋巴细胞相关蛋白4(抗CTLA-4)开始,ICIs(现在还包括针对程序性细胞死亡的抗体1(PD-1)及其配体( PD-L1)-迅速获得了美国食品和药物管理局的批准,可用于治疗多种癌症,这证明了患者生存的空前扩展。但是,尽管ICI取得了成功,但对这些药物的耐药性限制了能够获得持久应答的患者数量,并且免疫相关的不良事件使治疗变得复杂。因此,需要更好地理解ICI治疗后对有效和安全的抗肿瘤免疫反应的要求。对ICI治疗后免疫系统的肿瘤和全身性变化的研究已经为了解功效和耐药性的基础提供了见识。最终,通过利用这些见识,研究人员应该能够将ICI与其他药物结合,或设计新的免疫疗法,以实现更广泛,更持久的功效以及更高的安全性。在这里,我们回顾了ICI的历史和临床应用,对治疗的抗性机制以及与结果相关的局部和全身免疫细胞变化。

更新日期:2021-01-28
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