<i>Parvimonas micra</i> -polarized M2-like tumor-associated macrophages accelerate colorectal cancer development via IL-8 secretion

<i>Parvimonas micra</i> (<i>Pm</i>), a periodontal pathogen, has been implicated in the impairment of anti-tumor responses in colorectal cancer (CRC). The tumor microenvironment in CRC involves tumor-associated macrophages (TAMs), which are pivotal in modulating tumor-associated immune responses. The polarization of TAMs towards an M2-like phenotype promotes CRC progression by suppressing the immune system. However, the mechanisms by which <i>Pm</i> affects the progression of CRC remain inadequately elucidated. In this study, we explored the impact of <i>Pm</i> infection on CRC cell characteristics, including proliferation, chemoresistance, migration, and macrophage polarization. We found that <i>Pm</i>-infected THP-1-derived macrophages exhibited elevated interleukin-10 levels, a well-established M2 marker. Conditioned media from <i>Pm</i>-treated THP-1 cells significantly enhanced CRC cell proliferation, cisplatin resistance, and migration, and interleukin-8 was identified as a key factor. Consistent with the in vitro results, an azoxymethane/dextran sodium sulfate mouse model treated with oral <i>Pm</i> showed accelerated CRC tumor growth. These results offer mechanistic insights into the influence of <i>Pm</i> infection on tumor microenvironment in CRC through M2-like macrophage polarization. The identified pathways may serve as potential targets for therapeutic interventions for CRC.