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Cancer coopts differentiation of B-cell precursors into macrophages [human]

ABSTRACT: We recently reported that some cancers induce accumulation of bone marrow (BM) B-cell precursors in the spleen to convert them into metastasis-promoting, immunosuppressive B cells. Here, using various murine tumor models and samples from humans with breast and ovarian cancers, we provide evidence that cancer cells also coopt differentiation of the extranodal B-cell precursors to generate macrophages (termed B-MF). We link the trans-differentiation to a small subset of CSF1R+ Pax5Lo cells within BM pro-/pre-B and immature B cells and cancer-secreted M-CSF that downregulates Pax5 via CSF1R signaling. Thus, cancer generates tumor-associated macrophages (TAM) from B-cell precursors besides their primary source, monocytes. Based on their differences from monocyte-derived TAM, such as a superb ability to induce FoxP3+ Tregs, suppress proliferation of T cells and more efficiently phagocytize apoptotic cells, we propose that cancer generates B-MF to mediate cancer escape.

ORGANISM(S): Homo sapiens

PROVIDER: GSE180284 | GEO | 2021/09/20

REPOSITORIES: GEO

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Cancer coopts differentiation of B-cell precursors into macrophages [mouse]

Project description:We recently reported that some cancers induce accumulation of bone marrow (BM) B-cell precursors in the spleen to convert them into metastasis-promoting, immunosuppressive B cells. Here, using various murine tumor models and samples from humans with breast and ovarian cancers, we provide evidence that cancer cells also coopt differentiation of the extranodal B-cell precursors to generate macrophages (termed B-MF). We link the trans-differentiation to a small subset of CSF1R+ Pax5Lo cells within BM pro-/pre-B and immature B cells and cancer-secreted M-CSF that downregulates Pax5 via CSF1R signaling. Thus, cancer generates tumor-associated macrophages (TAM) from B-cell precursors besides their primary source, monocytes. Based on their differences from monocyte-derived TAM, such as a superb ability to induce FoxP3+ Tregs, suppress proliferation of T cells and more efficiently phagocytize apoptotic cells, we propose that cancer generates B-MF to mediate cancer escape.

2021-09-20 | GSE180283 | GEO

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RNA-seq analysis of gene expression in macrophages progenitors from the yolk sac of murine embryos at embryonic days 9 and 10, and the modifications resulting from a defective expression of the transcription factor Lyl-1

Project description:Most resident macrophages (MF) populations in adult tissues arise from MF progenitors populations that emerge during ontogeny, either from haematopoietic stem cells (HSC), or from Yolk Sac (YS) progenitors produced prior to HSC development. The YS generates two populations of MF progenitors. In the earliest one, called primitive, MF progenitors arise from monopotent/uni-lineage progenitors, while in the second one they derive from multipotent erythro-myeloid progenitors. These two populations soon mix in the blood circulation, and as they are highly similar in phenotype, the specific features and function of the two MF progenitors populations are still unclear. When investigating the function of the bHLH transcription factor Lyl-1 during the development of blood cells in mouse embryos, we observed that Lyl-1 expression marks YS primitive MF progenitors. Lyl-1 bHLH disruption leads to an increased production and a defective differentiation of primitive MF progenitors. To gain a better insight into primitive MF progenitors specificity and function, we performed a RNA-seq analysis of these progenitors sorted from the YS at embryonic day (E) 9, when the YS only contains primitive MF progenitors, and at E10, when it contains both primitive MF progenitors and those produced by erythro-myeloid progenitors. At both stages, MF progenitors were collected from the YS of either wild-type or Lyl-1-deficient embryos, to better understand the role of Lyl-1 in the development of Lyl-1-expressing resident macrophage populations.

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