Translocation of Helicobacter hepaticus synergizes with myeloid-derived suppressor cells and contributes to breast carcinogenesis

OncoImmunology

James G. Fox¹  Zhengchuan Niu¹  Huan Deng²  Susan Erdman³  Sureshkumar Muthupalani³  Haibo Liu⁴  Timothy C. Wang⁴ 

[1] Surgeons, Columbia University, New York, NY, USA;Department of Pathology, The Fourth Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China;Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA;;Division of Digestive and Liver Diseases and Herbert Irving Cancer Research Center, Vagelos College of Physicians &

关键词: Intestinal dysbiosis;    Helicobacter hepaticus;    breast cancer;    infection;    myeloid-derived suppressor cell;    histidine decarboxylase;   

DOI  :  10.1080/2162402X.2022.2057399

来源: DOAJ

【 摘 要 】

Microbial dysbiosis plays an important role in the development of intestinal diseases. Recent studies suggest a link between intestinal bacteria and mammary cancer. Here, we report that female ApcMin/+ mice infected with Helicobacter hepaticus exhibited an increased mammary and small/large intestine tumor burden compared with uninfected littermates. H. hepaticus DNA was detected in small/large intestine, mammary tumors, and adjacent lymph nodes, suggesting a migration pathway. CD11b+Gr1+ myeloid-derived suppressor cells (MDSCs) infiltrated and expressed high levels of Wnts, likely enhancing tumorigenesis through activation of Wnt/β-catenin pathway. Our previous studies indicated that histidine decarboxylase (Hdc) marks a population of myeloid-biased hematopoietic stem cells and granulocytic MDSCs. Cytokines/chemokines secreted by IL-17-expressing mast cells and tumor tissues promoted Hdc+ MDSCs expansion and trafficking toward mammary tumors. Adoptive transfer of MDSCs isolated from H. hepaticus-infected mice increased MDSCs frequencies in peripheral blood, mesenteric lymph nodes, mammary gland, and lymph nodes in recipient ApcMin/+ mice. The adoptive transfer of H. hepaticus primed MDSCs also increased the size and number of mammary tumors. Our results demonstrate that H. hepaticus can translocate from the intestine to mammary tissues to promote mammary tumorigenesis with MDSCs. Targeting bacteria and MDSCs may be useful for the prevention and therapy of extraintestinal cancers.Abbreviations: Helicobacter hepaticus, Hh; myeloid-derived suppressor cell, MDSC; histidine decarboxylase, Hdc; Breast cancer, BC; T regulatory, TR; inflammatory bowel disease, IBD; fluorescence in situ hybridization, FISH; myeloid-biased hematopoietic stem cells, MB-HSCs; granulocytic MDSCs, PMN-MDSCs; Lipopolysaccharide, LPS; Toll-like receptors, TLRs; Mast cells, MCs; Granulocyte-macrophage colony-stimulating factor, GM-CSF; epithelial–mesenchymal transition, EMT; Intestinal epithelial cells, IECs.

【 授权许可】

Unknown