期刊
SIGNAL TRANSDUCTION AND TARGETED THERAPY
卷 6, 期 1, 页码 -出版社
SPRINGERNATURE
DOI: 10.1038/s41392-021-00795-x
关键词
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资金
- National Natural Science Foundation of China [8177100280, 81730102, 81972221, 81702037]
- Science and Technology Commission of Shanghai [20ZR1442800]
- Clinical research plan of SHDC [SHDC2020CR2069B, SHDC2020CR5006-002, SHDC12019114]
The research found that high levels of F. nucleatum are associated with improved therapeutic responses to PD-1 blockade in patients with CRC, and F. nucleatum also enhances the antitumor effects of PD-L1 blockade on CRC. Furthermore, F. nucleatum induces PD-L1 expression and increases the accumulation of interferon-gamma (IFN-gamma)(+) CD8(+) tumor-infiltrating lymphocytes.
Given that only a subset of patients with colorectal cancer (CRC) benefit from immune checkpoint therapy, efforts are ongoing to identify markers that predict immunotherapeutic response. Increasing evidence suggests that microbes influence the efficacy of cancer therapies. Fusobacterium nucleatum induces different immune responses in CRC with different microsatellite-instability (MSI) statuses. Here, we investigated the effect of F. nucleatum on anti-PD-L1 therapy in CRC. We found that high F. nucleatum levels correlate with improved therapeutic responses to PD-1 blockade in patients with CRC. Additionally, F. nucleatum enhanced the antitumor effects of PD-L1 blockade on CRC in mice and prolonged survival. Combining F. nucleatum supplementation with immunotherapy rescued the therapeutic effects of PD-L1 blockade. Furthermore, F. nucleatum induced PD-L1 expression by activating STING signaling and increased the accumulation of interferon-gamma (IFN-gamma)(+) CD8(+) tumor-infiltrating lymphocytes (TILs) during treatment with PD-L1 blockade, thereby augmenting tumor sensitivity to PD-L1 blockade. Finally, patient-derived organoid models demonstrated that increased F. nucleatum levels correlated with an improved therapeutic response to PD-L1 blockade. These findings suggest that F. nucleatum may modulate immune checkpoint therapy for CRC.
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