微生物癌症免疫疗法重新编程造血以增强髓细胞驱动的抗肿瘤免疫，这一成果由美国威尔康奈尔医学院Michael S. Glickman研究团队经过不懈努力而取得。该研究于2025年5月29日发表于国际一流学术期刊《癌细胞》杂志上。

研究人员证明，在膀胱中施用卡介苗定殖骨髓，并在小鼠和人类中重新编程HSPCs以改变和扩增骨髓生成。BCG重编程的HSPCs足以通过产生中性粒细胞、单核细胞和树突状细胞来增强抗肿瘤免疫，这些细胞广泛地重塑肿瘤微环境，驱动T细胞依赖性抗肿瘤反应，并与检查点阻断协同作用。该团队得出结论，膀胱BCG通过造血系统起作用，突出了HSPC重编程增强T细胞依赖性肿瘤免疫先天驱动的广泛潜力。

据介绍，牛分枝杆菌卡介苗（BCG）是预防结核病的疫苗和膀胱癌的免疫疗法。当静脉注射卡介苗时，卡介苗重新编程骨髓造血干细胞和祖细胞（HSPCs），导致异源细胞保护它们免受感染。HSPC重编程是否有助于膀胱注射卡介苗的抗肿瘤作用尚不清楚。

附：英文原文

Title: Microbial cancer immunotherapy reprograms hematopoiesis to enhance myeloid-driven anti-tumor immunity

Author: Andrew W. Daman, Anthony C. Antonelli, Gil Redelman-Sidi, Lucinda Paddock, Shireen Khayat, Mythili Ketavarapu, Jin Gyu Cheong, Leonardo F. Jurado, Anna Benjamin, Song Jiang, Dughan Ahimovic, Victoria R. Lawless, Michael J. Bale, Oleg Loutochin, Victor A. McPherson, Maziar Divangahi, Rachel E. Niec, Dana Pe’er, Eugene Pietzak, Steven Z. Josefowicz, Michael S. Glickman

Issue&Volume: 2025-05-29

Abstract: Mycobacterium bovis Bacillus Calmette-Guérin (BCG) is the vaccine against tuberculosis and an immunotherapy for bladder cancer. When administered intravenously, BCG reprograms bone marrow hematopoietic stem and progenitor cells (HSPCs), leading to heterologous protection against infections. Whether HSPC reprogramming contributes to the anti-tumor effects of BCG administered into the bladder is unknown. We demonstrate that BCG administered in the bladder colonizes the bone marrow and, in both mice and humans, reprograms HSPCs to alter and amplify myelopoiesis. BCG-reprogrammed HSPCs are sufficient to confer augmented anti-tumor immunity through production of neutrophils, monocytes, and dendritic cells that broadly remodel the tumor microenvironment, drive T cell-dependent anti-tumor responses, and synergize with checkpoint blockade. We conclude that bladder BCG acts systemically through hematopoiesis, highlighting the broad potential of HSPC reprogramming to enhance the innate drivers of T cell-dependent tumor immunity.

DOI: 10.1016/j.ccell.2025.05.002

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(25)00211-9