Faecalibacterium prausnitzii promotes anti-PD-L1 efficacy in natural killer/T-cell lymphoma by enhancing antitumor immunity

作者：Zhuangzhuang Shi, Wenxing Jiang, Hongwen Li, Yue Zhang, Weili Xue, Yingjun Wang, Mingzhi Zhang, Zhaoming Li · 发表于：BMC Medicine · 年份：2025 · DOI：10.1186/s12916-025-04230-8 · 被引用次数：14 · 研究领域：Gut microbiota and health、Probiotics and Fermented Foods、Immune Cell Function and Interaction

BACKGROUND: Natural killer/T-cell lymphoma (NKTCL) is a highly aggressive subtype of lymphoma characterized by a poor prognosis. While immune checkpoint blockade (ICB) therapy has emerged as an effective treatment modality for various cancers, its efficacy among individuals is inconsistent and remains suboptimal for the majority of NKTCL patients. Faecalibacterium prausnitzii, recognized as a next-generation probiotic with immunomodulatory capabilities, has not yet been fully explored for its potential to influence the outcomes of ICB therapy. METHODS: We established syngeneic tumor-bearing mouse models of NKTCL and treated the mice with an anti-PD-L1 monoclonal antibody (mAb) and F. prausnitzii. Metabolomics analysis was performed to quantify butyrate concentrations in fecal, plasma, and tumor samples from the mice. Furthermore, we used flow cytometry, multiplex immunohistochemistry, and enzyme-linked immunosorbent assays to assess the effects of butyrate supplementation on antitumor immune responses in mice receiving anti-PD-L1 therapy. Additionally, an antibiotic-pretreated mouse model was utilized to further investigate the influence of F. prausnitzii on the efficacy of ICB therapy. RESULTS: The combination of F. prausnitzii and an anti-PD-L1 mAb effectively inhibited tumor growth, primarily through the action of its metabolite butyrate. Notably, F. prausnitzii-derived butyrate played a crucial role in enhancing the efficacy of ICB therapy by augmenting antitumor immune r...