肿瘤细胞治疗研究
英文原题：Tumor microbiome-transcriptome crosstalk identifies Prevotella as an immunotherapeutic predictor in NSCLC.
背景：肿瘤驻留微生物组在塑造肿瘤免疫微环境中起关键作用；然而，其在非小细胞肺癌（NSCLC）中与宿主转录组及免疫检查点抑制剂（ICIs）应答的关系仍很大程度上未被阐明。
背景：肿瘤驻留微生物组在塑造肿瘤免疫微环境中发挥关键作用；然而，其在非小细胞肺癌（NSCLC）中与宿主转录组及免疫检查点抑制剂（ICIs）应答的关系在很大程度上仍未得到表征。本研究旨在阐明NSCLC中组织驻留微生物群、宿主转录组改变与免疫治疗应答之间的关系。方法：采用2bRAD-M和bulk RNA测序对NSCLC患者的配对肿瘤（T）和癌旁组织（PT）样本进行分析，以生成全面的微生物组和转录组图谱。采用条件互信息算法系统研究瘤内微生物-宿主相互作用。在四个独立的本地临床队列中评估关键微生物与患者预后、ICI应答及表皮生长因子受体（EGFR）靶向治疗应答之间的关联。结果：PT样本中观察到比T样本更高的微生物丰富度、α多样性和β多样性。具体而言，PT驻留的Bradyrhizobium和Prevotella被确定为与免疫细胞群体（包括CD8+ T细胞、NK 细胞和活化树突状细胞）显著相关的关键细菌类群。其中，PT驻留的Prevotella（而非Bradyrhizobium）在本地临床数据集和公共数据集中均与NSCLC患者预后改善及ICI应答独立相关。此外，将PT驻留Prevotella丰度与常规临床血液指标整合的联合诊断模型，在预测ICI应答方面表现出明显优于传统生物标志物PD-L1的性能。相比之下，PT定植的普雷沃菌属与EGFR靶向治疗队列中的治疗反应无关联。结论：PT定植的普雷沃菌属与NSCLC患者的预后及ICI反应密切相关。此外，将PT定植的普雷沃菌属与常规临床血液指标相结合，有望作为一种潜在的辅助诊断工具，以促进NSCLC的个性化免疫治疗。
Background: The tumor-resident microbiome plays a pivotal role in shaping the tumor immune microenvironment; however, its relationship with the host transcriptome and the response to immune checkpoint inhibitors (ICIs) remains largely uncharacterized in non-small cell lung cancer (NSCLC). This study aimed to elucidate the relationship between tissue-resident microbiota, host transcriptomic alterations, and immunotherapy response in NSCLC. Methods: Paired tumor (T) and paracancerous tissue (PT) samples from patients with NSCLC were analyzed using 2bRAD-M and bulk RNA sequencing to generate comprehensive microbiome and transcriptome profiles. The conditional mutual information algorithm was employed to systematically investigate intratumoral microbe-host interactions. Associations between key microbes and patient prognosis, ICI response, and response to epidermal growth factor receptor ( EGFR )-targeted therapy were assessed across four independent local clinical cohorts. Results: Higher microbial richness, α-diversity, and β-diversity were observed in PT samples than in T samples. Specifically, PT-resident Bradyrhizobium and Prevotella were identified as key bacterial taxa significantly associated with immune cell populations, including CD8 + T cells, natural killer cells, and activated dendritic cells. Among these, PT-resident Prevotella , but not Bradyrhizobium , was independently associated with improved prognosis of patients with NSCLC and ICI response in both local clinical sets and public datasets. Furthermore, a combined diagnostic model integrating PT-resident Prevotella abundance with routine clinical blood indicators demonstrated markedly superior predictive performance for ICI response compared with the conventional biomarker PD-L1. By contrast, PT-resident Prevotella exhibited no association with treatment response in the EGFR -targeted therapy cohort. Conclusion: PT-resident Prevotella is strongly associated with the prognosis and ICI response in patients with NSCLC. Moreover, integration of PT-resident Prevotella with routine clinical blood indicators holds promise as a potential auxiliary diagnostic tool to facilitate personalized immunotherapy in NSCLC.
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