Fares Charlene M, Van Allen Eliezer M, Drake Charles G, Allison James P, Hu-Lieskovan Siwen
1 Department of Medicine, Division of Hematology/Oncology, University of California, Los Angeles, Los Angeles, CA.
2 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Am Soc Clin Oncol Educ Book. 2019 Jan;39:147-164. doi: 10.1200/EDBK_240837. Epub 2019 May 17.
The emergence of immune checkpoint blockade therapies over the last decade has transformed cancer treatment in a wide range of tumor types. Unprecedented and durable clinical responses in difficult-to-treat cancer histologies have been observed. However, despite these promising long-term responses, the majority of patients fail to respond to immune checkpoint blockade, demonstrating primary resistance. Additionally, many of those who initially respond to treatment eventually experience relapse secondary to acquired resistance. Both primary and acquired resistance are a result of complex and constantly evolving interactions between cancer cells and the immune system. Many mechanisms of resistance have been characterized to date, and more continue to be uncovered. By elucidating and targeting mechanisms of resistance, treatments can be tailored to improve clinical outcomes. This review will discuss the landscape of immune checkpoint blockade response data, different resistance mechanisms, and potential therapeutic strategies to overcome resistance.
在过去十年中，免疫检查点阻断疗法的出现改变了多种肿瘤类型的癌症治疗方式。在难以治疗的癌症组织学中观察到了前所未有的持久临床反应。然而，尽管有这些令人鼓舞的长期反应，但大多数患者对免疫检查点阻断无反应，表现出原发性耐药。此外，许多最初对治疗有反应的患者最终会因获得性耐药而复发。原发性和获得性耐药都是癌细胞与免疫系统之间复杂且不断演变的相互作用的结果。迄今为止，许多耐药机制已被阐明，并且更多的机制仍在不断被发现。通过阐明和靶向耐药机制，可以定制治疗方案以改善临床结果。本综述将讨论免疫检查点阻断反应数据的情况、不同的耐药机制以及克服耐药的潜在治疗策略。
