Amuc_1434 From Akkermansia muciniphila Enhances CD8+ T Cell‐Mediated Anti‐Tumor Immunity by Suppressing PD‐L1 in Colorectal Cancer

ABSTRACT Colorectal cancer (CRC) shows a limited response to programmed death‐ligand 1 (PD‐L1) immunotherapies. Akkermansia muciniphila (AKK) may enhance tumor immunity. This study examines how its Outer Membrane Vesicles (OMVs) and Amuc_1434 influence PD‐L1 expression and CD8+ T cell activity in CRC. OMVs were isolated and their characteristics were examined through transmission electron microscopy and Western blotting. PD‐L1 expression was quantified via Western blot, while CD8+ T cell proliferation was measured using flow cytometry. Cytokine production (interferon‐gamma (IFN‐γ) and interleukin‐2 (IL‐2)) was evaluated using ELISA. A CRC mouse model was employed to examine its impact on tumor growth and immune cell infiltration. In CRC cells, treatment with AKK‐derived OMVs (AKK‐OMVs) significantly downregulated PD‐L1 expression ( p < 0.05) and markedly increased CD8+ T cell proliferation and the levels of IFN‐γ and IL‐2 ( p < 0.01). Amuc_1434 was identified as the key protein mediating these effects. In vivo, AKK‐OMVs treatment substantially reduced tumor volume ( p < 0.01) and significantly enhanced CD8+ T cell infiltration into the tumor microenvironment ( p < 0.01). Additionally, AKK‐OMVs‐treated mice showed increased expression of immune activation markers within the tumor tissue, further indicating enhanced antitumor immunity. This study reveals that AKK‐OMVs, particularly those containing Amuc_1434, can modulate PD‐L1 expression and potentiate CD8+ T cell‐mediated antitumor immunity in CRC. These findings suggest a novel approach to overcoming resistance to immune checkpoint inhibitors in CRC.