iProXProteomicsShengbo HanHomo Sapienshttp://www.iprox.org/page/project.html?id=IPX0014973000shengbohan1@163.comHuazhong University of Science and TechnologyiProXFusobacterium nucleatum is a key microbial driver of colorectal cancer progression. In this study, we identified an intercellular signaling axis through which F. nucleatum remodels the immune microenvironment. Analysis of 54 clinical colorectal cancer specimens revealed that high intratumoral F. nucleatum load correlated significantly with PD-L1 upregulation in tumor-associated macrophages, diminished CD8+ T-cell cytotoxicity, and poor patient prognosis. Mechanistically, F. nucleatum infection activated NF-κB signaling in colorectal cancer cells to induce the transcription of the long noncoding RNA mitotically associated long noncoding RNA (MANCR), which was selectively packaged into exosomes via the ESCRT-III/ALIX complex and transferred to macrophages. In recipient macrophages, exosomal MANCR interacted with HNRNP U to increase PD-L1 mRNA stability, leading to sustained PD-L1 surface expression. In humanized mouse models, F. nucleatum exposure inhibited CD8+ T-cell infiltration and suppressed granzyme B activity, thereby compromising antitumor immunity and facilitating tumor proliferation and metastasis. These findings demonstrate that F. nucleatum exploits a tumor-derived exosomal long noncoding RNA network to remotely manipulate macrophage plasticity. Therefore, targeting the F. nucleatum/MANCR/PD-L1 axis may represent a viable strategy to overcome immune resistance in the colorectal cancer microenvironment.<h4>Significance</h4>Fusobacterium nucleatum exploits tumor-derived exosomal MANCR to stabilize PD-L1 in macrophages, providing a mechanism of bacterial-driven immune evasion and a potential therapeutic target to restore antitumor immunity in colorectal cancer.Fusobacterium nucleatum Promotes Exosomal LncRNA MANCR Secretion from Colorectal Cancer Cells to Induce PD-L1 Expression in Macrophages.Han Shengbo S, Lv Guozheng G, Hu Ping P, Hu Yuhang Y, Zeng Zhu Z, Liu Xinghua X, Zhao Yong Y, Li Yang Y, Huang Yan Y, Zhao Yingsong Y, Zhuo Wenfeng W, Wang Hongda H, Zhao Eryang E, Zhao Guangyu G, Hu Rong R, Zhao Gang GfalseFusobacterium nucleatum Promotes PD-L1 Expression in Macrophages by Inducing Exosomal lncRNA MANCR from Colorectal Cancer CellsThis mass spectrometry dataset was generated from RNA pull-down assays to identify proteins interacting with lncRNA MANCR in colorectal cancer cells (HCT116) and macrophages (THP-1)Sun Jan 04 00:00:00 GMT 2026PXD072638960642202059