加拿大麦吉尔大学Maziar Divangahi小组的一项最新研究开发出了一种真菌衍生的佐剂通过重编程颗粒生成增强了卡介苗芽孢杆菌的抗肿瘤效力。相关论文发表在2025年6月23日出版的《免疫学》杂志上。

使用临床前原位膀胱癌模型，小组发现单次膀胱内联合BCG和β-葡聚糖免疫治疗根除侵袭性肿瘤，达到100%的生存率。通过单细胞转录组学/表观基因组学分析、流式细胞术和活体成像，该课题组发现卡介苗和β-葡聚糖对造血干细胞和祖细胞进行了重编程，并在先天免疫细胞，特别是中性粒细胞中留下印记。重编程中性粒细胞表现出活性氧（ROS）的产生增加和肿瘤核心的浸润，减少肿瘤的血管化和生长。肿瘤微环境可将中性粒细胞转化为肿瘤原细胞；卡介苗和β-葡聚糖阻止了这种转化，促进了持续的抗肿瘤活性。这些发现支持β-葡聚糖作为一种安全、有效的佐剂，增强卡介苗对膀胱癌和其他实体肿瘤的免疫治疗。

据悉，在非细胞浸润性膀胱癌患者中，标准的免疫治疗包括膀胱内卡介苗（BCG）。然而，它的成功需要反复给药，约50%的患者没有获益。

附：英文原文

Title: A fungal-derived adjuvant amplifies the antitumoral potency of Bacillus Calmette-Guérin via reprogramming granulopoiesis

Author: Leonardo F. Jurado, Andrew W. Daman, Ziyi Li, Vanessa M.S. Ross, Kristina Nikolaou, Kim A. Tran, Oleg Loutochin, Victor A. McPherson, Renaud Prével, Raquel Tarancón, Katalina Couto, Erwan Pernet, Nargis Khan, Jin-Gyu Cheong, Reshma Ramaiah, Mythili Ketavarapu, Eva Kaufmann, Michael S. Glickman, Ajitha Thanabalasuriar, Steven Z. Josefowicz, Maziar Divangahi

Issue&Volume: 2025-06-23

Abstract: In patients with non-muscle invasive bladder cancer, the standard immunotherapy involves intravesical Bacillus Calmette-Guérin (BCG). However, its success requires repeated doses, and ～50% of patients do not benefit. Using a preclinical orthotopic bladder cancer model, we found that a single intravesical dose of combined BCG and β-glucan immunotherapy eradicated aggressive tumors, resulting in 100% survival. Through single-cell transcriptomic/epigenomic analysis, flow cytometry, and intravital imaging, we show that BCG and β-glucan reprogrammed hematopoietic stem and progenitor cells with imprinting in innate immune cells, particularly neutrophils. Reprogrammed neutrophils exhibited increased reactive oxygen species (ROS) production and infiltration into the tumor core, reducing tumor vascularization and growth. The tumor microenvironment can convert neutrophils into protumor cells; BCG and β-glucan prevented this conversion, promoting sustained antitumoral activity. These findings support β-glucan as a safe, effective adjuvant to enhance BCG immunotherapy in bladder cancer and other solid tumors.

DOI: 10.1016/j.immuni.2025.05.026

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00247-X