Microbial cancer immunotherapy reprograms hematopoiesis to enhance myeloid-driven anti-tumor immunity Journal Article

   

Authors:	Daman, A. W.; Antonelli, A. C.; Redelman-Sidi, G.; Paddock, L.; Khayat, S.; Ketavarapu, M.; Cheong, J. G.; Jurado, L. F.; Benjamin, A.; Jiang, S.; Ahimovic, D.; Lawless, V. R.; Bale, M. J.; Loutochin, O.; McPherson, V. A.; Divangahi, M.; Niec, R. E.; Pe'er, D.; Pietzak, E.; Josefowicz, S. Z.; Glickman, M. S.
Article Title:	Microbial cancer immunotherapy reprograms hematopoiesis to enhance myeloid-driven anti-tumor immunity
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. © 2025 Elsevier Inc.
Keywords:	bladder cancer; immunotherapy; epigenetics; tumor immunity; hematopoiesis; bcg; innate immune memory; trained immunity
Journal Title:	Cancer Cell
Volume:	43
Issue:	8
ISSN:	1535-6108
Publisher:	Cell Press
Publication status:	Published
Date Published:	2025-08-11
Online Publication Date:	2025-05-29
Start Page:	1442
End Page:	1459.e10
Language:	English
DOI:	10.1016/j.ccell.2025.05.002
PROVIDER:	scopus
PMCID:	PMC12377364
PUBMED:	40446799
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-105006986167&doi=10.1016%2fj.ccell.2025.05.002&partnerID=40&md5=ccde48e9356bbb1a29fd16054429f12a
Notes:	Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Michael Glickman -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/228203