| First Author | Chen C | Year | 2022 |
| Journal | Nat Commun | Volume | 13 |
| Issue | 1 | Pages | 5376 |
| PubMed ID | 36104343 | Mgi Jnum | J:336688 |
| Mgi Id | MGI:7340838 | Doi | 10.1038/s41467-022-33117-y |
| Citation | Chen C, et al. (2022) Cancer co-opts differentiation of B-cell precursors into macrophage-like cells. Nat Commun 13(1):5376 |
| abstractText | We have 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 cancers also co-opt differentiation of these B-cell precursors to generate macrophage-like cells (termed B-MF). We link the transdifferentiation to a small subset of CSF1R(+) Pax5(Low) cells within BM pre-B and immature B cells responding to cancer-secreted M-CSF with downregulation of the transcription factor Pax5 via CSF1R signaling. Although the primary source of tumor-associated macrophages is monocytes, B-MFs are phenotypically and functionally distinguishable. Compared to monocyte-derived macrophages, B-MFs more efficiently phagocytize apoptotic cells, suppress proliferation of T cells and induce FoxP3(+) regulatory T cells. In mouse tumor models, B-MFs promote shrinkage of the tumor-infiltrating IFNgamma(+) CD4 T cell pool and increase cancer progression and metastasis, suggesting that this cancer-induced transdifferentiation pathway is functionally relevant and hence could serve as an immunotherapeutic target. |
