Department of Colorectal Surgery, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, 312000, Zhejiang Province, PR China.
Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou 310014, Zhejiang Province, PR China; Clinical Research Institute, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou 310014, Zhejiang Province, PR China.
Immunol Lett. 2020 May;221:61-71. doi: 10.1016/j.imlet.2020.02.008. Epub 2020 Feb 22.
Within the past decade, immune-checkpoint inhibitors (ICPIs), including anti-programmed cell death 1 (PD-1), anti-programmed cell death 1 ligand 1 (PD-L1), and anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) antibodies, are undoubtfully the most remarkable advances in cancer therapy. The immune responses are modulated by these ICPIs via blocking the inhibitory PD-1/PD-L1 path and result in immune activation in the suppressive microenvironment of the tumor. While ICPIs result in benefits for numerous patients with malignancy and lead to disease control and survival, toxicity and safety problems have emerged as well. Although immune mediated adverse effects due to ICPIs could involve any organ system, skin, endocrine glands, and gastrointestinal tract, are one of the most commonly affected. Fortunately, in most of the cases, these immune‑mediated adverse effects (imAEs) are manageable, while in some cases these toxicities are fulminant and fatal and lead to the withdrawal of treatment. Numerous attempts have been started and are continuing to reduce the incidence rate of imAEs. Further studies are required for a better understanding of these imAEs, decrease the occurrence, and lighten the severity. In this work, we overview the imAEs and also, highlight the most important aspects of the imAEs management.
在过去的十年中，免疫检查点抑制剂（ICPIs），包括抗程序性细胞死亡蛋白 1（PD-1）、抗程序性细胞死亡蛋白 1 配体 1（PD-L1）和抗细胞毒性 T 淋巴细胞相关抗原 4（CTLA-4）抗体，无疑是癌症治疗中最显著的进展。这些 ICPIs 通过阻断抑制性 PD-1/PD-L1 途径来调节免疫反应，导致肿瘤抑制微环境中的免疫激活。虽然 ICPIs 为许多恶性肿瘤患者带来了益处，导致疾病控制和生存，但也出现了毒性和安全性问题。虽然由于 ICPIs 引起的免疫介导的不良反应（imAEs）可能涉及任何器官系统，但皮肤、内分泌腺和胃肠道是最常受影响的器官之一。幸运的是，在大多数情况下，这些免疫介导的不良反应（imAEs）是可管理的，而在某些情况下，这些毒性是暴发性和致命的，并导致治疗中断。已经开始并正在继续进行许多尝试，以降低 imAEs 的发生率。需要进一步的研究来更好地了解这些 imAEs，减少其发生并减轻其严重程度。在这项工作中，我们综述了 imAEs，并强调了 imAEs 管理的最重要方面。
