Lachnoclostridium intestinal flora is associated with immunotherapy efficacy in nasopharyngeal carcinoma

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

doi:10.1002/hed.27917

Lachnoclostridium intestinal flora is associated with immunotherapy efficacy in nasopharyngeal carcinoma

Head Neck. 2024 Aug 12. doi: 10.1002/hed.27917. Online ahead of print.

Authors

Zikun Yu^{1

2}, Qin Wang^{1

2}, Zimeng Wang^{1

2}, Sihan Liu^{1

2}, Tianliang Xia^{1

2}, Chongyang Duan³, Youping Liu^{1

4}, Xi Ding^{1

2}, Siyuan Chen^{1

2}, Tao Yu^{1

2}, Rui You^{1

4}, Mingyuan Chen^{1

4}, Peiyu Huang^{1

2}

Affiliations

¹ 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.
² Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, China.
³ Department of Biostatistics, School of Public Health, Southern Medical University, Guangzhou, China.
⁴ Nasopharyngeal Cancer Prevention Center, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, China.

PMID: 39135356
DOI: 10.1002/hed.27917

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.

Keywords: Lachnoclostridium; gut microbiome; immunotherapy; nasopharyngeal carcinoma.

Abstract

Grants and funding