GEO series

B cell leukemia co-opts a hematopoietic stem cell-CD4 T cell tolerance program that facilitates relapse [scATAC-Seq]

GSE262391 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 4 samples Submitted 2025/12/31 Platform GPL24247

Summary

Despite advances in immune therapies, leukemic relapse is still a major obstacle to long-term survival. Using a murine model of B cell leukemia (B-ALL), we show that B-ALL co-opts a hematopoetic stem cell (HSC)-driven program to induce immune-suppressive type-1 regulatory (Tr1) CD4 T cells. The immune-suppressive function of Tr1s that protects healthy HSCs is utilized by B-ALL to evade T-cell surveillance. Using single-cell approaches, we show that B-ALL induces a Tr1 phenotype in all CD4 T cells irrespective of their initial polarization state. Unlike exhausted T cells, Tr1s do not have epigenetic silencing of effector cytokines. Both IL10R- and PDL1-blockade mitigate Tr1 expansion upon treatment with the tyrosine kinase inhibitor nilotinib. However, PDL1-blockade alone expands Th1-memory CD4s and effector CD8s that prevent relapse. We find a similar population of CD4 Tr1s in human B-ALL patients, which correlate with worse prognosis. Thus, B-ALL co-opts an HSC-driven program to induce Tr1s that suppress anti-leukemia T cell responses, which facilitates relapse.

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Also filed as BioProject PRJNA1091641 and SRA study SRP497666. Searching any of these in the dataset finder brings you back here.

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