-glucan. We found that TNBC was associated with extramedullary erythropoiesis and expansion of CECs. Unexpectedly, curdlan worsened tumor progression by further increasing CEC abundance. Immunophenotypic analysis revealed a marked expansion of Galectin-3 (Gal-3)+ CECs in both spleen and tumor. Mechanistically, our findings suggest that curdlan-Dectin-1ligation induces Gal-3 shedding from CD11b+cells, enabling its deposition onto CECs. Notably, we discovered that Gal-3 is co-expressed and colocalized with PD-L1 and Dectin-1 on CECs. Importantly, PD-L1 blockade substantially reduced immunosuppressive Gal-3+PD-L1+ CECs, suppressed extramedullary erythropoiesis, and induced pronounced tumor regression. Re-analysis of publicly available scRNAseq datasets further confirmed the abundance of Gal-3+ CECs in human bone marrow. Collectively, these findings identify Gal-3+PD-L1+ CECs as key drivers of an immunosuppressive tumor microenvironment and reveal a previously unrecognized axis through which PD-L1 blockade exerts therapeutic benefit in breast cancer.
Azimi et al. (Tue,) studied this question.