先前的观察表明，局部晚期直肠癌（LARC）患者对新辅助放化疗（nCRT）的反应存在很大差异。最近针对结直肠癌瘤内微生物群的研究揭示了其在肿瘤发生和肿瘤进展中的作用。然而，有限的研究集中在肿瘤内微生物群对 LARC nCRT 的影响上。我们使用来自已发表的欧洲队列的 RNA-seq 数据探索了 LARC 肿瘤微环境中的微生物谱。在病理完全缓解 (pCR) 和非 pCR 组中对微生物特征进行了表征。对瘤内微生物组和转录组进行多组学分析。pCR 组和非 pCR 组的微生物 α 和 β 多样性存在显着差异。在 pCR 组和非 pCR 组之间发现了 12 种差异微生物，其中 6 种与与细胞外基质形成相关的癌症相关成纤维细胞 (CAF) 亚群有关。基于七种差异微生物相对丰度的微生物风险评分对 nCRT 反应具有预测价值（AUC = 0.820，p< 0.001）。我们的研究将瘤内微生物作为 nCRT 对 LARC 反应的潜在独立预测标记，并证明了肿瘤内微生物和 CAF 之间的相互作用介导 nCRT 反应的潜在机制。版权所有 © 2023 Sun, Qu, Ke, Zhuang, Xu, Lv, Leng, Zhuang,guan, Feng and Sun.

Previous observations have demonstrated that the response to neoadjuvant chemoradiotherapy (nCRT) is highly variable in patients with locally advanced rectal cancer (LARC). Recent studies focusing on the intratumoral microbiota of colorectal cancer have revealed its role in oncogenesis and tumor progression. However, limited research has focused on the influence of intratumoral microbiota on the nCRT of LARC.We explored the microbial profiles in the tumor microenvironment of LARC using RNA-seq data from a published European cohort. Microbial signatures were characterized in pathological complete response (pCR) and non-pCR groups. Multi-omics analysis was performed between intratumor microbiomes and transcriptomes.Microbial α and β diversity were significantly different in pCR and non-pCR groups. Twelve differential microbes were discovered between the pCR and non-pCR groups, six of which were related to subclusters of cancer-associated fibroblasts (CAFs) associated with extracellular matrix formation. A microbial risk score based on the relative abundance of seven differential microbes had predictive value for the nCRT response (AUC = 0.820, p < 0.001).Our study presents intratumoral microbes as potential independent predictive markers for the response of nCRT to LARC and demonstrates the underlying mechanism by which the interaction between intratumoral microbes and CAFs mediates the response to nCRT.Copyright © 2023 Sun, Qu, Ke, Zhang, Xu, Lv, Leng, Zhang, Guan, Feng and Sun.