Bruton's tyrosine kinase (BTK) and indoleamine 2,3-dioxygenase (IDO) block differentiation of inflammatory dendritic cells in tumors [scRNA-seq]

Dendritic cells (DCs) are pivotal drivers of anti-tumor immunity, but many of the DCs in tumors appear dysfunctional or immunosuppressive. Using mouse models, we found that robustly immunogenic DCs can arise by differentiation from immature myeloid precursor cells during inflammation. In tumors, however, differentiation of these inflammatory DCs was blocked by a cell-intrinsic signaling pathway created by Bruton's Tyrosine Kinase (BTK) and the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO). Overall design: B16F10 tumors were treated with cyclophosphamide (CTX)/ibrutinib/indoximod, and cells isolated from TDLNs 48 hrs after the dose of CTX. Separate libraries were contructed for the two biological replicate mice in each treatment group, then pooled for scRNA-seq.