肠道菌群中的迟缓梭菌属与鼻咽癌免疫治疗疗效相关。

Lachnoclostridium intestinal flora is associated with immunotherapy efficacy in nasopharyngeal carcinoma.

作者信息

Yu Zikun, Wang Qin, Wang Zimeng, Liu Sihan, Xia Tianliang, Duan Chongyang, Liu Youping, Ding Xi, Chen Siyuan, Yu Tao, You Rui, Chen Mingyuan, Huang Peiyu

机构信息

State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.

Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, China.

出版信息

Head Neck. 2025 Jan;47(1):269-281. doi: 10.1002/hed.27917. Epub 2024 Aug 12.

DOI:10.1002/hed.27917

PMID:39135356

Abstract

BACKGROUND

Effective biomarkers for assessing anti-PD-1/PD-L1 therapy efficacy in patients with nasopharyngeal carcinoma (NPC) are still lacking. The human gut microbiota has been shown to influence clinical response to anti-PD-1/PD-L1 therapy in many cancers. However, the relationship between the gut microbiota and the efficacy of immunotherapy in patients with nasopharyngeal carcinoma has not been determined.

METHODS

We conducted a prospective study in which fecal and blood samples from patients with NPC were subjected to 16S rDNA sequencing and survival analysis. To investigate potential differences in the gut microbiome between these groups and to identify potential biomarkers indicative of immunotherapy efficacy, patients were categorized into two groups according to their clinical response to immunotherapy, the responder group (R group) and the non-responder group (NR group). Progression-free survival (PFS) between these subgroups was analyzed using Kaplan-Meier survival analysis with the log-rank test. Additionally, we performed univariate and multivariate analyses to evaluate prognostic factors. Finally, we carried out non-targeted metabolomics to examine the metabolic effects associated with the identified microbiome.

RESULTS

Our 16S rDNA sequencing results showed that the abundance of Lachnoclostridium was higher in the NR group than in the R group (p = 0.003), and alpha diversity analysis showed that the abundance of microbiota in the NR group was higher than that in the R group (p = 0.050). Patients with a lower abundance of Lachnoclostridium had better PFS (p = 0.048). Univariate (p = 0.017) and multivariate analysis (p = 0.040) showed that Lachnoclostridium was a predictor of PFS. Non-targeted metabolomics analysis revealed that Lachnoclostridium affects the efficacy of immunotherapy through the usnic acid.

CONCLUSIONS

High abundance of Lachnoclostridium predicts poor prognosis in patients with NPC receiving immunotherapy.

摘要

背景

评估鼻咽癌（NPC）患者抗PD-1/PD-L1治疗疗效的有效生物标志物仍然缺乏。已表明人类肠道微生物群会影响许多癌症患者对抗PD-1/PD-L1治疗的临床反应。然而，肠道微生物群与鼻咽癌患者免疫治疗疗效之间的关系尚未确定。

方法

我们进行了一项前瞻性研究，对鼻咽癌患者的粪便和血液样本进行16S rDNA测序和生存分析。为了研究这些组之间肠道微生物群的潜在差异，并确定指示免疫治疗疗效的潜在生物标志物，根据患者对免疫治疗的临床反应将其分为两组，即反应者组（R组）和无反应者组（NR组）。使用Kaplan-Meier生存分析和对数秩检验分析这些亚组之间的无进展生存期（PFS）。此外，我们进行了单变量和多变量分析以评估预后因素。最后，我们进行了非靶向代谢组学分析，以检查与鉴定出的微生物群相关的代谢效应。

结果

我们的16S rDNA测序结果显示，NR组中拉克诺梭菌的丰度高于R组（p = 0.003），α多样性分析显示NR组中微生物群的丰度高于R组（p = 0.050）。拉克诺梭菌丰度较低的患者具有更好的PFS（p = 0.048）。单变量分析（p = 0.017）和多变量分析（p = 0.040）表明，拉克诺梭菌是PFS的一个预测指标。非靶向代谢组学分析表明，拉克诺梭菌通过松萝酸影响免疫治疗的疗效。