Microbial cancer immunotherapy reprograms hematopoietic stem cells to enhance anti-tumor immunity.
Andrew W DamanAnthony C AntonelliGil Redelman-SidiLucinda PaddockJin Gyu CheongLeonardo F JuradoAnna BenjaminSong JiangDughan AhimovicShireen KhayatMichael J BaleOleg LoutochinVictor A McPhersonDana Pe'erMaziar DivangahiEugene J PietzakSteven Zvi JosefowiczMichael S GlickmanPublished in: bioRxiv : the preprint server for biology (2024)
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 intratumor dendritic cell infiltration, reprograms pro-tumorigenic neutrophils, 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.
Keyphrases
- bone marrow
- spinal cord injury
- stem cells
- dendritic cells
- high fat diet induced
- mycobacterium tuberculosis
- mesenchymal stem cells
- dna damage
- cell therapy
- regulatory t cells
- microbial community
- signaling pathway
- single cell
- emergency department
- acute myeloid leukemia
- insulin resistance
- hiv infected
- oxidative stress
- cell cycle
- skeletal muscle
- wild type
- climate change