Study on the mechanism by which myeloid-derived suppressor cells expressing histidine decarboxylase promote the development of breast cancer in mice with intestinal flora dysbiosis

Although intestinal dysbiosis (ID) contributes to gastrointestinal diseases including tumor, direct evidence for ID involving the tumorigenesis of non-intestinal organs is lacking. The innate immunity in response to ID can recruit tumor-associated neutrophils (TANs) to promote mammary cancer process. However, whether its progenitors, granulocytic myeloid-derived suppressor cells (PMN-MDSCs), serve as essential component during this process is largely unknown. Our preliminary results indicated that, in the setting of ID, bacterium can translocate to mammary cancer tissue and increase the frequency of PMN-MDSCs, which express high level of histidine decarboxylase (Hdc). Thus, we propose that ID promotes the translocation of intestinal bacterium to mammary gland and recruits Hdc+ PMN-MDSCs, which in turn secret Wnts to activate Wnt/β-catenin and finally result in the malignant transformation of mammary tubular epithelium. To test this, we will mainly conduct fluorescence in situ hybridization (FISH), RNA-seq, and adoptive transfer to explore the exact pathway of bacterial translocation and the underlying molecular mechanisms by which Hdc+ PMN-MDSCs exert effects on mammary cancerogenesis, providing mechanistic insights into treating ID-associated tumors.