Microbial cancer immunotherapy reprograms hematopoietic stem cells to enhance anti-tumor immunity.

TitleMicrobial cancer immunotherapy reprograms hematopoietic stem cells to enhance anti-tumor immunity.
Publication TypeJournal Article
Year of Publication2024
AuthorsDaman AW, Antonelli AC, Redelman-Sidi G, Paddock L, Cheong JGyu, Jurado LF, Benjamin A, Jiang S, Ahimovic D, Khayat S, Bale MJ, Loutochin O, McPherson VA, Pe'er D, Divangahi M, Pietzak E, Josefowicz SZ, Glickman MS
Date Published2024 Mar 21

UNLABELLED: Mycobacterium bovis 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 in both mice and humans reprograms HSPCs to amplify myelopoiesis and functionally enhance myeloid cell antigen presentation pathways. Reconstitution of naive mice with HSPCs from bladder BCG-treated mice enhances anti-tumor immunity and tumor control, increases intratumoral dendritic cell infiltration, and synergizes with checkpoint blockade. We conclude that bladder BCG acts systemically, reprogramming HSPC-encoded innate immunity, highlighting the broad potential of modulating HSPC phenotypes to improve tumor immunity.

ONE SENTENCE SUMMARY: BCG administered in the bladder reprograms bone marrow HSPCs and contributes to tumor control via enhanced myeloid cells.

Alternate JournalbioRxiv
PubMed ID38562703
PubMed Central IDPMC10983927
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