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

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. This gene expression microarray study examines differences between PBMC-derived B cells from breast cancer (BC, N=8) and non-diseased (ND, N=7) patients