Background: Preclinical and clinical data indicate that chemoradiotherapy (CRT) in combination with checkpoint inhibitors may prime an anti-tumor immunological response in esophageal cancer. However, responses to neoadjuvant therapy can vary widely and the key biomarkers to determine response remain poorly understood. The fecal microbiome is a novel and potentially modifiable biomarker of immunotherapy response, and both fecal and tumor microbes have been found to associate with outcomes in esophageal cancer.Methods:Fecal and tumor samples were collected from patients with stage II–III resectable esophageal or gastroesophageal junction carcinoma treated with neoadjuvant immune checkpoint inhibitors (ICIs) plus CRT prior to surgical resection. Microbiome profiles were analyzed by 16S rRNA amplicon sequencing and taxonomic data were integrated with fecal metabolite analysis to assess microbial function.Results: The fecal microbiome of patients with pathological complete response (PCR) grouped in distinct clusters compared to patients with residual viable tumor (RVT) by Bray–Curtis diversity metric. Integrated taxonomic and metabolomic analysis of fecal samples identified a sphingolipid and primary bile acid as enriched in the PCR, the levels of which correlated with several bacterial species:Roseburis inulinivorans, Ruminococcus callidus,andFusicantenibacter saccharivorans.Analysis of the tumor microbiome profiles identified several bacterial genera previously associated with esophageal tumors, includingStreptococcusandVeillonella.Conclusions: These results further characterize the fecal and tumor microbiome of patients with operable esophageal cancer and identify specific microbes and metabolites that may help elucidate how microbes contribute to tumor response with neoadjuvant CRT combined with ICI.
背景：临床前及临床数据显示，放化疗联合检查点抑制剂可能激发食管癌的抗肿瘤免疫反应。然而，新辅助治疗的应答反应差异显著，且决定应答的关键生物标志物仍不明确。粪便微生物组作为免疫治疗应答的新型且可调控的生物标志物，其与食管癌预后的关联性已在粪便及肿瘤微生物中得到证实。 方法：本研究收集了II–III期可切除食管癌或胃食管结合部癌患者的粪便及肿瘤样本，这些患者均在手术切除前接受了新辅助免疫检查点抑制剂联合放化疗治疗。通过16S rRNA扩增子测序分析微生物组特征，并将分类学数据与粪便代谢物分析相结合，以评估微生物功能。 结果：基于Bray–Curtis多样性指数分析，病理完全缓解患者的粪便微生物组与残留存活肿瘤患者的微生物组呈现明显不同的聚类特征。对粪便样本的综合分类学与代谢组学分析发现，鞘脂类及初级胆汁酸在病理完全缓解患者中富集，其水平与多种细菌物种相关：包括Roseburis inulinivorans、Ruminococcus callidus及Fusicantenibacter saccharivorans。肿瘤微生物组分析识别出多种先前与食管肿瘤相关的细菌属，包括链球菌属和韦荣球菌属。 结论：本研究进一步描述了可手术食管癌患者粪便及肿瘤微生物组的特征，并识别出特定的微生物及代谢物，有助于阐明微生物在新辅助放化疗联合免疫检查点抑制剂治疗中如何影响肿瘤应答。
肿瘤(癌症)患者之家