The IL-6/JAK/STAT3 pathway is aberrantly hyperactivated in many types of cancer, and such hyperactivation is generally associated with a poor clinical prognosis. In the tumour microenvironment, IL-6/JAK/STAT3 signalling acts to drive the proliferation, survival, invasiveness, and metastasis of tumour cells, while strongly suppressing the antitumour immune response. Thus, treatments that target the IL-6/JAK/STAT3 pathway in patients with cancer are poised to provide therapeutic benefit by directly inhibiting tumour cell growth and by stimulating antitumour immunity. Agents targeting IL-6, the IL-6 receptor, or JAKs have already received FDA approval for the treatment of inflammatory conditions or myeloproliferative neoplasms and for the management of certain adverse effects of chimeric antigen receptor T cells, and are being further evaluated in patients with haematopoietic malignancies and in those with solid tumours. Novel inhibitors of the IL-6/JAK/STAT3 pathway, including STAT3-selective inhibitors, are currently in development. Herein, we review the role of IL-6/JAK/STAT3 signalling in the tumour microenvironment and the status of preclinical and clinical investigations of agents targeting this pathway. We also discuss the potential of combining IL-6/JAK/STAT3 inhibitors with currently approved therapeutic agents directed against immune-checkpoint inhibitors.

IL-6 / JAK / STAT3途径在许多类型的癌症中异常地过度活化，并且这种过度活化通常与不良的临床预后相关。在肿瘤微环境中，IL-6 / JAK / STAT3信号传导起着驱动肿瘤细胞增殖，存活，侵袭和转移的作用，同时强烈抑制了抗肿瘤免疫反应。因此，针对癌症患者中IL-6 / JAK / STAT3途径的治疗有望通过直接抑制肿瘤细胞生长和刺激抗肿瘤免疫力来提供治疗益处。靶向IL-6，IL-6受体或JAK的药物已获得FDA的批准，可用于治疗炎症或骨髓增生性肿瘤，并用于控制嵌合抗原受体T细胞的某些不良反应，并正在对造血系统恶性肿瘤和实体瘤患者进行进一步评估。目前正在开发IL-6 / JAK / STAT3途径的新型抑制剂，包括STAT3选择性抑制剂。本文中，我们综述了IL-6 / JAK / STAT3信号传导在肿瘤微环境中的作用以及针对该途径的药物的临床前和临床研究状况。我们还讨论了将IL-6 / JAK / STAT3抑制剂与目前批准的针对免疫检查点抑制剂的治疗剂结合的潜力。我们回顾了IL-6 / JAK / STAT3信号在肿瘤微环境中的作用以及针对该途径的药物的临床前和临床研究状况。我们还讨论了将IL-6 / JAK / STAT3抑制剂与目前批准的针对免疫检查点抑制剂的治疗剂结合的潜力。我们回顾了IL-6 / JAK / STAT3信号在肿瘤微环境中的作用以及针对该途径的药物的临床前和临床研究状况。我们还讨论了将IL-6 / JAK / STAT3抑制剂与目前批准的针对免疫检查点抑制剂的治疗剂结合的潜力。