Checkpoint blockade toxicities: Insights into autoimmunity and treatment.
Checkpoint blockade toxicities: Insights into autoimmunity and treatment.
复制标题
检查点封锁毒性：对自身免疫和治疗的见解。
DOI：
10.1016/j.smim.2021.101473
复制
发表时间：
2021
影响因子：
7.8
通讯作者：
Dougan,Michael
中科院分区：
文献类型：
--
作者：
Walsh,MichaelJ;Dougan,Michael
检查点封锁不仅改变了癌症的治疗方式，还突显了针对肿瘤建立适当免疫反应的重要性。尽管免疫治疗领域取得了进展，但许多患者出现了一系列炎症毒性，限制了这些治疗的疗效。这些毒性从屏障部位损伤，如结肠炎，到内分泌器官功能障碍，如糖尿病。为了正确治疗癌症患者，避免检查站封锁引起的毒副作用，我们必须更深入地了解产生这些不良事件的潜在机制。细胞毒性和组织驻留的T细胞可能在介导某些毒性中发挥重要作用，尽管在其他毒性中高水平的细胞因子和自身抗体的产生表明这些机制并不都是相同的。考虑到与检查站封锁相关的风险收益，针对特定毒性的某些风险因素可能能够预测谁可能从替代疗法中受益最大。由于检查点抑制剂的靶点在预防自身免疫中具有重要作用，深入了解危险因素和毒性原因将加深我们对基础免疫学的认识，并使新的治疗方法的开发成为可能。
Checkpoint blockade has transformed not only the way cancers are treated, but also highlighted the importance of mounting a proper immune response against tumors. Despite advances in the field of immunotherapy, many patients develop a range of inflammatory toxicities that limit the efficacy of these therapies. These toxicities range from barrier site injury, such as colitis, to endocrine organ dysfunction, such as diabetes. In order to properly treat patients with cancer and avoid checkpoint blockade induced toxicities, we must gain a deeper understanding of the underlying mechanisms generating these adverse events. Cytotoxic and tissue-resident T cells likely play an important role in mediating some toxicities, though high levels of cytokines and the generation of auto-antibodies in other toxicities demonstrates these mechanisms are not all shared. Certain risk factors for specific toxicities may be able to predict who might benefit most from alternative therapies given the risk-benefit associated with checkpoint blockade. As the targets of checkpoint inhibitors have important functions in the prevention of autoimmunity, insights into risk factors and causes of toxicities will further our knowledge of fundamental immunology and enable the development of novel therapeutics.