AUTHOR=Gu Jinhua , Lv Xiaojun , Li Wenwen , Li Guangcai , He Xialian , Zhang Ye , Shi Lihong , Zhang Xiaoqian 

TITLE=Deciphering the mechanism of Peptostreptococcus anaerobius-induced chemoresistance in colorectal cancer: the important roles of MDSC recruitment and EMT activation

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1230681

DOI=10.3389/fimmu.2023.1230681

ISSN=1664-3224

ABSTRACT=<p><italic>Peptostreptococcus anaerobius</italic> (<italic>P. anaerobius</italic>, <italic>PA</italic>) in intestinal flora of patients with colorectal cancer (CRC) are associated with poor prognosis. Studies have shown that <italic>P. anaerobius</italic> could promote colorectal carcinogenesis and progression, but whether <italic>P. anaerobius</italic> could induce chemoresistance of colorectal cancer has not been clarified. Here, both <italic>in vitro</italic> and <italic>in vivo</italic> experiments showed that <italic>P. anaerobius</italic> specifically colonized the CRC lesion and enhanced chemoresistance of colorectal cancer to oxaliplatin by recruiting myeloid-derived suppressor cells (MDSCs) into the tumor microenvironment. Furthermore, this study revealed that it was the increased secretion of IL-23 by MDSCs that subsequently facilitated the epithelial–mesenchymal transition (EMT) of tumor cells to induce chemoresistance of CRC by activating the Stat3-EMT pathway. Our results highlight that targeting <italic>P. anaerobius</italic> might be a novel therapeutic strategy to overcome chemoresistance in the treatment of CRC.</p>