Cancer promotes immune escape via transdifferentiating B cells into macrophage-like cells

Abstract 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, secretes TSLP cause premature emigration B-cell precursors from bone marrow (BM) accumulation in spleen as a source tBregs 3. However, it remains unclear why other cancers similarly precursors, although they not generate tBregs. Here, report this is use these macrophage-like (termed B-MF) 4. We found transdifferentiate small but bona fide Csf1R +Pax5 Lowsubsets BM B cells(pre-B immature IgM cells) into B-MF tumor. This alternative pathway tumor-associated macrophages (TAM) phenotypically functionally distinguishable monocyte-derived TAMs, B-MFs more efficiently phagocytize apoptotic cells, suppress proliferation T induce +regulatory cells. Our modeling studies mice with reveal support tumor progression presumably by retarding tumor-infiltrating IFNγ +CD4 +T Since B-MF-like their transcriptional signature can be detected patients ovarian cancers, think transdifferentiation clinically relevant hence could serve an immunotherapeutic target. work was supported Intramural Research Program, NIA/NIH.