目前最常用的免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)包括程序性细胞死亡蛋白1配体1(programmed cell death protein 1 ligand 1,PD-1 PD-L1)抑制剂和细胞毒性T淋巴细胞相关抗原4(cy-totoxic T lymphocyte-associated ant...目前最常用的免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)包括程序性细胞死亡蛋白1配体1(programmed cell death protein 1 ligand 1,PD-1 PD-L1)抑制剂和细胞毒性T淋巴细胞相关抗原4(cy-totoxic T lymphocyte-associated antigen 4,CTLA-4)抑制剂,是近年来食管癌治疗的重大突破,为食管癌患者带来显著生存获益的同时,也会诱发肺炎、内分泌系统紊乱、心肌炎等一系列免疫相关不良事件(immune-related adverse events,irAEs)[1-2]。irAEs产生作用机制尚不明确,可能为免疫检查点抑制剂在治疗食管癌的同时,引起自身免疫系统的激活,免疫细胞过度活跃、促进炎症的细胞因子增多和自身免疫抗体增多,作用过程中对机体正常细胞、组织及器官产生一定的损害,出现相关不良事件。展开更多
抗程序性细胞死亡受体-1(programmed cell death protein-1,PD-1)和抗程序性死亡受体配体-1(programmed cell death ligand-1,PD-L1)是目前广泛使用的免疫检查点抑制剂,在肿瘤免疫治疗方面取得了巨大的成就,但同时也导致免疫相关不良反...抗程序性细胞死亡受体-1(programmed cell death protein-1,PD-1)和抗程序性死亡受体配体-1(programmed cell death ligand-1,PD-L1)是目前广泛使用的免疫检查点抑制剂,在肿瘤免疫治疗方面取得了巨大的成就,但同时也导致免疫相关不良反应(immune-related adverse events,irAEs),严重者甚至会导致患者死亡。因此,明确irAEs的发生机制,提早预测irAEs非常重要。本文由细胞、免疫系统、个体水平层面对抗PD-1/PD-L1疗法致irAEs的发生机制进行了总结,并从一般临床特征、免疫细胞因素、细胞因子相关、基因表达结果等方面汇总了irAEs的预测指标。展开更多
随着免疫检查点抑制剂(ICIs)在肿瘤治疗领域的广泛应用,其引发的免疫相关不良反应(irAEs)也备受关注。irAEs可发生于全身任何器官系统,其中以肌肉骨骼表现为主的风湿性irAEs在临床中常有报道,如炎性关节炎、风湿性多肌痛、肌炎、血管炎...随着免疫检查点抑制剂(ICIs)在肿瘤治疗领域的广泛应用,其引发的免疫相关不良反应(irAEs)也备受关注。irAEs可发生于全身任何器官系统,其中以肌肉骨骼表现为主的风湿性irAEs在临床中常有报道,如炎性关节炎、风湿性多肌痛、肌炎、血管炎等,早期识别和干预此类不良反应对改善肿瘤患者预后尤为重要,而寻找有助于精确预测irAEs发生的生物标志物也成为未来研究的热点。因此,本文就ICIs相关风湿性不良反应的临床特点、诊断和鉴别诊断、管理及潜在预测性标志物加以综述,以加强临床医师对此类疾病的认识。With the wide application of immune checkpoint inhibitors (ICIs) in the field of tumor therapy, the immune-related adverse events (irAEs) induced by ICIs have also attracted much attention. The irAEs can occur in any organ system, among which rheumatic irAEs which are mainly characterized by musculoskeletal manifestations have often been reported in clinic, such as inflammatory arthritis, polymyalgia rheumatica, myositis, vasculitis. Early identification and intervention of these adverse events are important for improving prognosis of cancer patients. Finding biomarkers that can help to accurately predict the development of irAEs will be a focus of future research. Therefore, this article reviews the clinical features, diagnosis, differential diagnosis, management and potential predictive markers of ICIs-associated rheumatic adverse events to enhance clinicians’ understanding of these diseases.展开更多
恶性肿瘤的免疫治疗是当前肿瘤研究和治疗领域的热点,免疫检查点分子程序性死亡受体-1(programmed cell death receptor-1,PD-1)和细胞毒性T淋巴细胞相关抗原4(cytotoxic T lymphocyte-associated antigen 4,CTLA-4)相关信号通路的激活...恶性肿瘤的免疫治疗是当前肿瘤研究和治疗领域的热点,免疫检查点分子程序性死亡受体-1(programmed cell death receptor-1,PD-1)和细胞毒性T淋巴细胞相关抗原4(cytotoxic T lymphocyte-associated antigen 4,CTLA-4)相关信号通路的激活可以抑制T淋巴细胞活化,肿瘤细胞通过激活该信号通路实现免疫逃逸。免疫检查点抑制剂(immuno-checkpoint inhibitors,ICIs)通过抑制该信号通路,活化T淋巴细胞发挥机体对肿瘤细胞的清除。因此,ICIs的相关毒性包括免疫相关的不良事件(immune-related adverse effects,irAEs)。消化系统如胃肠道、肝脏作为人体重要的消化吸收器官、代谢解毒器官,同时也是重要的免疫相关器官,是irAEs的常见受累系统。本文将分别对ICIs的肝脏、胃肠道不良反应的发生率、临床表现、诊断和处理分别进行阐述。展开更多
文摘抗程序性细胞死亡受体-1(programmed cell death protein-1,PD-1)和抗程序性死亡受体配体-1(programmed cell death ligand-1,PD-L1)是目前广泛使用的免疫检查点抑制剂,在肿瘤免疫治疗方面取得了巨大的成就,但同时也导致免疫相关不良反应(immune-related adverse events,irAEs),严重者甚至会导致患者死亡。因此,明确irAEs的发生机制,提早预测irAEs非常重要。本文由细胞、免疫系统、个体水平层面对抗PD-1/PD-L1疗法致irAEs的发生机制进行了总结,并从一般临床特征、免疫细胞因素、细胞因子相关、基因表达结果等方面汇总了irAEs的预测指标。
文摘随着免疫检查点抑制剂(ICIs)在肿瘤治疗领域的广泛应用,其引发的免疫相关不良反应(irAEs)也备受关注。irAEs可发生于全身任何器官系统,其中以肌肉骨骼表现为主的风湿性irAEs在临床中常有报道,如炎性关节炎、风湿性多肌痛、肌炎、血管炎等,早期识别和干预此类不良反应对改善肿瘤患者预后尤为重要,而寻找有助于精确预测irAEs发生的生物标志物也成为未来研究的热点。因此,本文就ICIs相关风湿性不良反应的临床特点、诊断和鉴别诊断、管理及潜在预测性标志物加以综述,以加强临床医师对此类疾病的认识。With the wide application of immune checkpoint inhibitors (ICIs) in the field of tumor therapy, the immune-related adverse events (irAEs) induced by ICIs have also attracted much attention. The irAEs can occur in any organ system, among which rheumatic irAEs which are mainly characterized by musculoskeletal manifestations have often been reported in clinic, such as inflammatory arthritis, polymyalgia rheumatica, myositis, vasculitis. Early identification and intervention of these adverse events are important for improving prognosis of cancer patients. Finding biomarkers that can help to accurately predict the development of irAEs will be a focus of future research. Therefore, this article reviews the clinical features, diagnosis, differential diagnosis, management and potential predictive markers of ICIs-associated rheumatic adverse events to enhance clinicians’ understanding of these diseases.
