免疫抑制剂联合治疗毒副反应相关最新进展分析

Recent Developments Related to the Toxic Side Effects of Immunosuppressive Combination Therapy

摘要: 恶性肿瘤是在发病率和死亡率方面仅次于心血管疾病的第二大类疾患，世界卫生组织国际癌症研究机构(International Agency for Research on Cancer, IARC)发布了2020年世界最新的癌症负担数据，全世界癌症新发病例总共1929万例，全球癌症死亡病例996万例，我国癌症新发病例占比23.7%，死亡病例占比30.2%，二者均位列第一。恶性肿瘤传统的常见治疗方式包括化学治疗、内分泌治疗、靶向治疗、放射治疗、外科手术治疗，但上述治疗模式已进入了停滞阶段。2018年，免疫治疗首次进入我国，相比于传统肿瘤疗法，免疫治疗可大幅提高患者的晚期生存率，尤其对于恶性黑色素瘤、肾癌及非小细胞肺癌患者，其生存率的提高效果更为明显，部分患者甚至可维持5~10年。尤其胸膜间皮瘤、小细胞肺癌、肝癌肿瘤中，突破了多年治疗无明显进展的局面，带来生存的获益。免疫治疗包括免疫检查点抑制剂和过继细胞治疗，通过操纵免疫系统来识别和攻击癌细胞。这些疗法有可能在多种实体和血液系统恶性肿瘤中诱导持久的反应，从而改变了对多种瘤种的治疗模式。其中，免疫检查点抑制剂(immune checkpoint inhibitors, ICI)为目前临床常用的免疫治疗模式之一，ICI包括程序化死亡受体-1 (programmed cell death protein-1, PD-1)/(programmed cell death-ligand 1, PD-L) 1和细胞毒性T淋巴细胞相关蛋白4 (cytotoxic T-lymphocyte-associated protein 4, CTLA-4)，同时在免疫检查点抑制剂引起的相关不良反应也不容忽视。本文为将对ICI相关的不良反应展开综述。

Abstract: Malignant neoplasm is the second most common type of disease after cardiovascular disease in terms of morbidity and mortality. The International Agency for Research on Cancer (IARC) of the World Health Organization has released the latest data on the burden of cancer in the world in 2020. The International Agency for Research on Cancer (IARC) released the latest data on the burden of cancer in the world in 2020, with a total of 19.29 million new cancer cases and 9.96 million cancer deaths worldwide. The traditional common treatment modalities for malignant tumors include chemotherapy, endocrine therapy, targeted therapy, radiation therapy, surgical treatment, but the above treatment modalities have entered a stagnant stage. In 2018, immunotherapy entered China for the first time, and compared with traditional tumor therapy, immunotherapy can significantly improve the late survival rate of patients, especially for patients with malignant melanoma, kidney cancer and non-small cell lung cancer. In particular, for patients with malignant melanoma, kidney cancer and non-small cell lung cancer, the improvement of survival rate is more obvious, and some patients can even sustain 5~10 years. Especially in pleural mesothelioma, small cell lung cancer and liver cancer tumors, the breakthrough of years of treatment without significant progress has brought survival benefits. Immunotherapy, which includes immune checkpoint inhibitors and per-icyte therapy, recognizes and attacks cancer cells by manipulating the immune system. These therapies have the potential to induce durable responses in a wide range of solid and hematologic malignancies, thus changing the treatment paradigm for a wide range of tumor types. Among them, immune checkpoint inhibitors (ICI) are one of the immunotherapy modalities commonly used in clinical practice, including programmed cell death receptor-1 (PD-1)/(programmed cell death-ligand 1 (PD-1)), Death-ligand 1 (PD-L) 1 and (cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)), and the associated adverse effects caused by immune checkpoint inhibitors should not be ignored. In this paper, we review the adverse effects associated with ICI.