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

Purpose: Given the potent immunostimulatory effects of bacterial outer membrane vesicles (OMVs) and the significant anti-colon tumor properties of Parabacteroides distasonis ( Pd ), this study aimed to elucidate the role and potential mechanisms of Pd -derived OMVs ( Pd -OMVs) against colon cancer.
Methods: This study isolated and purified Pd -OMVs from Pd cultures and assessed their characteristics. The effects of Pd -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 Pd -OMVs. Finally, we evaluated the biosafety of Pd -OMVs.
Results: Purified Pd -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 Pd -OMVs, resulting in a significant decrease in their proliferation and invasion abilities. Further in vivo studies confirmed the accumulation of Pd -OMVs in tumor tissues, which significantly inhibited the growth of colon tumors. Mechanistically, Pd -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, Pd -OMVs demonstrated a high level of biosafety.
Conclusion: This paper elucidates that Pd -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 Pd -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.
Competing Interests: The authors report no conflicts of interest in this work.
(© 2024 Liang et al.)