卡介苗免疫疗法的机制及其对膀胱癌的展望,Nature Reviews Urology

BCG免疫疗法是复发或进展风险高的非肌肉浸润性膀胱癌的金标准治疗。临床前和临床研究表明，对BCG的强烈炎症反应涉及几个步骤：BCG的附着；BCG内在化为常驻免疫细胞，正常细胞和肿瘤尿道上皮细胞；BCG介导的先天免疫的诱导，这是由细胞和细胞因子环境精心策划的；和BCG介导的肿瘤特异性免疫的启动。由于增加了复杂性，临床BCG菌株之间的变异可能会影响肿瘤免疫力的发展。但是，在首次将BCG用于膀胱癌后40多年，有关其作用机理的许多问题仍未得到解答。清楚地，更好地了解BCG介导的肿瘤免疫的潜在机制可以提高疗效，提高治疗耐受性，并鉴定出基于免疫的新疗法。实际上，由于靶向免疫疗法（包括检查点抑制剂）的可用性，对膀胱癌免疫疗法的热情以及将BCG与其他疗法结合的可能性正在增加。对BCG免疫疗法的作用机理的理解已大大提高，但是仍然存在许多问题，需要进一步的基础和临床研究工作来开发针对膀胱癌患者的新治疗策略。由于有针对性的免疫疗法，包括检查点抑制剂，可将BCG与其他疗法结合的可能性正在增加。对BCG免疫疗法的作用机理的理解已大大提高，但是仍然存在许多问题，需要进一步的基础和临床研究工作来开发针对膀胱癌患者的新治疗策略。由于有针对性的免疫疗法，包括检查点抑制剂，可将BCG与其他疗法结合的可能性正在增加。对BCG免疫疗法的作用机理的理解已大大提高，但是仍然存在许多问题，需要进一步的基础和临床研究工作来开发针对膀胱癌患者的新治疗策略。

"点击查看英文标题和摘要"

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.