Parabacteroides distasonis -Derived Outer Membrane Vesicles Enhance Antitumor Immunity Against Colon Tumors by Modulating CXCL10 and CD8 + T Cells

Given the potent immunostimulatory effects of bacterial outer membrane vesicles (OMVs) and the significant anti-colon tumor properties of ( ), this study aimed to elucidate the role and potential mechanisms of -derived OMVs ( -OMVs) against colon cancer. This study isolated and purified -OMVs from cultures and assessed their characteristics. The effects of -OMVs on CT26 cell uptake, proliferation, and invasion were investigated in vitro. In vivo, a CT26 colon tumor model was used to investigate the anti-colon tumor effects and underlying mechanisms of -OMVs. Finally, we evaluated the biosafety of -OMVs. Purified -OMVs had a uniform cup-shaped structure with an average size of 165.5 nm and a zeta potential of approximately -9.56 mV, and their proteins were associated with pathways related to immunity and apoptosis. In vitro experiments demonstrated that CT26 cells internalized the -OMVs, resulting in a significant decrease in their proliferation and invasion abilities. Further in vivo studies confirmed the accumulation of -OMVs in tumor tissues, which significantly inhibited the growth of colon tumors. Mechanistically, -OMVs increased the expression of CXCL10, promoting infiltration of CD8 T cells into tumor tissues and expression of pro-inflammatory factors TNF-α, IL-1β, and IL-6. Notably, -OMVs demonstrated a high level of biosafety. This paper elucidates that -OMVs can exert significant anti-colon tumor effects by upregulating the expression of the chemokine CXCL10, thereby increasing the infiltration of CD8 T cells into tumors and enhancing antitumor immune responses. This suggests that -OMVs may be developed as a novel nanoscale potent immunostimulant with great potential for application in tumor immunotherapy. As well as developed as a novel nano-delivery carrier for combination with other antitumor drugs.