研究概要
我们的研究表明,全身静脉注射 BCG 在肺肿瘤治疗中具有潜力,凸显其增强免疫反应和提升免疫检查点阻断疗效的能力。
中文摘要
膀胱内给予卡介苗(BCG)是美国食品药品监督管理局首批批准的免疫疗法之一,至今仍是膀胱癌标准治疗。既往研究表明,静脉注射BCG在动物中耐受性良好,并可有效预防结核感染。本研究在多种临床前肺肿瘤模型中评估静脉注射BCG。结果显示,在肺部黑色素瘤转移和原位肺腺癌模型中,BCG接种可抑制肿瘤生长并延长小鼠生存期。静脉BCG治疗耐受性良好,未见明显急性毒性。机制上,静脉BCG可诱导肿瘤特异性CD8+ T细胞应答,该应答依赖1型常规树突状细胞,同时也诱导NK细胞介导的免疫。最后,研究显示,在原本对抗PD-L1单药治疗耐药的小鼠肺肿瘤中,静脉BCG与抗PD-L1免疫检查点抑制剂联合具有叠加效果。总体而言,本研究展示了全身静脉给予BCG治疗肺肿瘤的潜力,强调其增强免疫应答和提高免疫检查点阻断疗效的能力。
展开英文摘要原文
Intravesical administration of Bacillus Calmette-Gu rin (BCG) was one of the first FDA-approved immunotherapies and remains a standard treatment for bladder cancer. Previous studies have demonstrated that intravenous (IV) administration of BCG is well-tolerated and effective in preventing tuberculosis infection in animals. Here, we examine IV BCG in several preclinical lung tumor models. Our findings demonstrate that BCG inoculation reduced tumor growth and prolonged mouse survival in models of lung melanoma metastasis and orthotopic lung adenocarcinoma. Moreover, IV BCG treatment was well-tolerated with no apparent signs of acute toxicity. Mechanistically, IV BCG induced tumor-specific CD8 + T cell responses, which were dependent on type 1 conventional dendritic cells, as well as NK cell-mediated immunity. Lastly, we also show that IV BCG has an additive effect on anti-PD-L1 checkpoint inhibitor treatment in mouse lung tumors that are otherwise resistant to anti-PD-L1 as monotherapy. Overall, our study demonstrates the potential of systemic IV BCG administration in the treatment of lung tumors, highlighting its ability to enhance immune responses and augment immune checkpoint blockade efficacy.
论文信息
- 作者
- Moreo E、Jarit-Cabanillas A、Robles-Vera I、Uranga S、Guerrero C、Gómez AB、Mata-Martínez P、Minute L
- 第一作者单位
- Grupo de Genética de Micobacterias, Departamento de Microbiología, Pediatría, Radiología y Salud Pública, Facultad de Medicina, Universidad de Zaragoza, IIS-Aragon, Zaragoza, Spain.Spain
- 通讯作者单位
- Grupo de Genética de Micobacterias, Departamento de Microbiología, Pediatría, Radiología y Salud Pública, Facultad de Medicina, Universidad de Zaragoza, IIS-Aragon, Zaragoza, Spain. naguilo@unizar.es.Spain
- 文献类型
- 非美国政府资助研究
- 期刊
- Nature communications2023 Oct 4