Department of Urology, Hôpital Européen Georges Pompidou, AP-HP, Paris Descartes University, Paris, France.
Unit of Dendritic Cell Immunobiology, Department of Immunology, Institut Pasteur, Paris, France.
Nat Rev Urol. 2018 Oct;15(10):615-625. doi: 10.1038/s41585-018-0055-4.
BCG immunotherapy is the gold-standard treatment for non-muscle-invasive bladder cancer at high risk of recurrence or progression. Preclinical and clinical studies have revealed that a robust inflammatory response to BCG involves several steps: attachment of BCG; internalization of BCG into resident immune cells, normal cells, and tumour urothelial cells; BCG-mediated induction of innate immunity, which is orchestrated by a cellular and cytokine milieu; and BCG-mediated initiation of tumour-specific immunity. As an added layer of complexity, variation between clinical BCG strains might influence development of tumour immunity. However, more than 40 years after the first use of BCG for bladder cancer, many questions regarding its mechanism of action remain unanswered. Clearly, a better understanding of the mechanisms underlying BCG-mediated tumour immunity could lead to improved efficacy, increased tolerance of treatment, and identification of novel immune-based therapies. Indeed, enthusiasm for bladder cancer immunotherapy, and the possibility of combining BCG with other therapies, is increasing owing to the availability of targeted immunotherapies, including checkpoint inhibitors. Understanding of the mechanism of action of BCG immunotherapy has advanced greatly, but many questions remain, and further basic and clinical research efforts are needed to develop new treatment strategies for patients with bladder cancer.
BCG 免疫疗法是高复发或进展风险的非肌肉浸润性膀胱癌的金标准治疗方法。临床前和临床研究表明,BCG 引起的强烈炎症反应涉及几个步骤:BCG 的附着;BCG 被内吞进入常驻免疫细胞、正常细胞和肿瘤尿路上皮细胞;BCG 介导的先天免疫的诱导,这是由细胞和细胞因子环境协调的;以及 BCG 介导的肿瘤特异性免疫的启动。作为一个额外的复杂性层次,临床 BCG 菌株之间的差异可能会影响肿瘤免疫的发展。然而,在首次使用 BCG 治疗膀胱癌 40 多年后,其作用机制仍有许多未解之谜。显然,更好地了解 BCG 介导的肿瘤免疫机制可以提高疗效、提高治疗耐受性,并确定新的免疫治疗方法。事实上,由于靶向免疫疗法(包括检查点抑制剂)的出现,人们对膀胱癌免疫疗法的热情以及将 BCG 与其他疗法联合使用的可能性正在增加。对 BCG 免疫疗法作用机制的理解已经有了很大的进展,但仍有许多问题悬而未决,需要进一步进行基础和临床研究,为膀胱癌患者开发新的治疗策略。