Division of Gastroenterology and Department of Medicine, Massachusetts General Hospital, and Harvard Medical School, Boston, MA 02114, USA.
Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Department of Immunology, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA.
Cell. 2021 Mar 18;184(6):1575-1588. doi: 10.1016/j.cell.2021.02.011. Epub 2021 Mar 5.
During the past decade, immunotherapies have made a major impact on the treatment of diverse types of cancer. Inflammatory toxicities are not only a major concern for Food and Drug Administration (FDA)-approved checkpoint blockade and chimeric antigen receptor (CAR) T cell therapies, but also limit the development and use of combination therapies. Fundamentally, these adverse events highlight the intricate balance of pro- and anti-inflammatory pathways that regulate protective immune responses. Here, we discuss the cellular and molecular mechanisms of inflammatory adverse events, current approaches to treatment, as well as opportunities for the design of immunotherapies that limit such inflammatory toxicities while preserving anti-tumor efficacy.
在过去的十年中,免疫疗法在治疗多种类型的癌症方面取得了重大进展。炎症毒性不仅是食品和药物管理局 (FDA) 批准的检查点阻断和嵌合抗原受体 (CAR) T 细胞疗法的主要关注点,而且还限制了联合疗法的发展和使用。从根本上讲,这些不良事件突出了调节保护性免疫反应的促炎和抗炎途径的复杂平衡。在这里,我们讨论了炎症不良事件的细胞和分子机制、当前的治疗方法,以及设计免疫疗法的机会,这些免疫疗法可以在保留抗肿瘤疗效的同时限制这种炎症毒性。