The incidence of cutaneous melanoma and the mortality rate of advanced melanoma patients continue to rise globally. Despite the recent success of immunotherapy including ipilimumab and pembrolizumab checkpoint inhibitors, a large proportion of patients are refractory to such treatment modalities. The application of mycobacteria such as Bacillus Calmette–Guérin (BCG) in the treatment of various malignancies, including cutaneous melanoma, has been clearly demonstrated after almost a century of observations and experimentation. Intralesional BCG (IL‐BCG) immunotherapy is a highly efficient and cost‐effective treatment option for inoperable stage III in‐transit melanoma, as recommended in the National Comprehensive Cancer Network Guidelines. IL‐BCG has shown great efficacy in the regression of directly injected metastatic melanoma lesions, as well as distal noninjected nodules in immunocompetent patients. Clinical and preclinical studies have shown that BCG serves as a strong immune modulator, inducing the recruitment of various immune cells that contribute to antitumour immunity. However, the specific mechanism of BCG‐mediated tumour immunity remains poorly understood. Comparative genome analyses have revealed that different BCG strains exhibit distinct immunological activity and virulence, which might impact the therapeutic response and clinical outcome of patients. In this review, we discuss the immunostimulatory potential of different BCG substrains and highlight clinical studies utilizing BCG immunotherapy for the treatment of cutaneous melanoma. Furthermore, the review focuses on the cellular and molecular mechanisms of the BCG‐induced immune responses of both the innate and adaptive arms of the immune system. Furthermore, the review discussed the administration of BCG as a monotherapy or in combination with other immunotherapeutic or chemotherapeutic agents.

中文翻译：

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黑色素瘤的BCG免疫疗法的临床和分子研究。

全球范围内，皮肤黑素瘤的发病率和晚期黑素瘤患者的死亡率持续上升。尽管最近获得了包括伊立木单抗和派姆单抗检查点抑制剂在内的免疫疗法的成功，但仍有很大一部分患者对这种治疗方式不敏感。经过近一个世纪的观察和实验，已经明确证明了分枝杆菌，例如卡介芽孢杆菌（BacillusCalmette-Guérin，BCG）在治疗各种恶性肿瘤（包括皮肤黑色素瘤）中的应用。正如《国家综合癌症网络指南》所建议的那样，IBS内免疫疗法是无法手术的III期转运中黑色素瘤的一种高效且具有成本效益的治疗选择。IL‐BCG在直接注射转移性黑色素瘤病变的消退中显示出巨大的功效，以及有免疫能力的患者的远端未注射结节。临床和临床前研究表明，BCG可作为一种强大的免疫调节剂，诱导募集各种有助于抗肿瘤免疫力的免疫细胞。然而，对BCG介导的肿瘤免疫的具体机制仍知之甚少。比较的基因组分析表明，不同的BCG菌株表现出独特的免疫活性和毒力，这可能会影响患者的治疗反应和临床结果。在这篇综述中，我们讨论了不同BCG亚株的免疫刺激潜力，并着重介绍了利用BCG免疫疗法治疗皮肤黑色素瘤的临床研究。此外，综述着重于BCG诱导免疫系统先天性和适应性臂的免疫反应的细胞和分子机制。此外，该评论讨论了卡介苗作为单一疗法或与其他免疫治疗或化学治疗剂联合使用的方法。