| Title: |
Cancer promotes immune escape via transdifferentiating B cells into macrophage-like cells |
| Authors: |
Biragyn, Arya; Chen, Chen; Park, Bongsoo; Bodogai, Monica; Lee, Jung-Min; Beerman, Isabel |
| Source: |
The Journal of Immunology ; volume 210, issue Supplement_1, page 169.10-169.10 ; ISSN 0022-1767 1550-6606 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2023 |
| Description: |
Previously we reported that breast cancer uses the generation of regulatory TGFb+ B cells to facilitate its metastasis via inducing FoxP3+Tregs and educating MDSCs 1,2. To do this, the cancer secretes TSLP to cause premature emigration of B-cell precursors from the bone marrow (BM) and accumulation in the spleen as a source of tBregs 3. However, it remains unclear why other cancers similarly cause premature emigration and accumulation of B-cell precursors, although they do not generate tBregs. Here, we report that this is to use these B-cell precursors to generate macrophage-like cells (termed B-MF) 4. We found that cancer transdifferentiate a small but bona fide Csf1R+Pax5Low subsets of BM B cells(pre-B and immature IgM+ B cells) into B-MF in the tumor. This alternative pathway of the generation of tumor-associated macrophages (TAM) is phenotypically and functionally distinguishable from that of BM monocyte-derived TAMs, as B-MFs more efficiently phagocytize apoptotic cells, suppress proliferation of T cells, and induce FoxP3+regulatory T cells. Our modeling studies in mice with cancer reveal that B-MFs support tumor progression and metastasis presumably by retarding tumor-infiltrating IFNγ+CD4+ T cells. Since B-MF-like cells and their transcriptional signature can be detected in patients with breast and ovarian cancers, we think that this transdifferentiation pathway is clinically relevant and hence could serve as an immunotherapeutic target. This work was supported by the Intramural Research Program, NIA/NIH. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.4049/jimmunol.210.supp.169.10 |
| Availability: |
https://doi.org/10.4049/jimmunol.210.supp.169.10; https://academic.oup.com/jimmunol/article-pdf/210/Supplement_1/169.10/61479230/169_10.pdf |
| Rights: |
https://academic.oup.com/pages/standard-publication-reuse-rights |
| Accession Number: |
edsbas.37A787E3 |
| Database: |
BASE |