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.

检查点封锁不仅改变了癌症的治疗方式，而且突出了对肿瘤进行适当免疫反应的重要性。尽管免疫疗法领域取得了进展，但许多患者会产生一系列炎症毒性，从而限制这些疗法的功效。这些毒性范围从屏障部位损伤（例如结肠炎）到内分泌器官功能障碍（例如糖尿病）。为了正确治疗癌症患者并避免检查点封锁引起的毒性，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 T 细胞可能在介导某些毒性中起重要作用，尽管高水平的细胞因子和其他毒性中自身抗体的产生表明这些机制并非全部共享。鉴于与检查点封锁相关的风险收益，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多。由于检查点抑制剂的靶点在预防自身免疫方面具有重要作用，对风险因素和毒性原因的深入了解将进一步加深我们对基础免疫学的了解，并促进新疗法的开发。