State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
J Dent Res. 2024 Sep;103(10):988-998. doi: 10.1177/00220345241262759. Epub 2024 Aug 5.
Most patients diagnosed with oral squamous cell carcinoma (OSCC) present with locally advanced stages, which are typically associated with poor outcomes. Although immunotherapy offers potential improvements in patient survival, its efficacy is hampered by low response rates. The microbiome is widely involved in tumor immunity and may play a role in immunotherapy. This study aimed to investigate the potential association between the oral (salivary) microbiome and immunotherapy response in patients with OSCC. Salivary metagenome sequencing was performed on 47 patients with OSCC undergoing neoadjuvant immunotherapy (NAIT) in a clinical trial (NCT04649476). Patients were divided into responders and nonresponders based on their pathological responses. The results showed that the species richness of the salivary microbiome was lower in the nonresponders before NAIT than in the responders. Differential analysis revealed that nonresponders exhibited a lower relative abundance of 34 bacterial species and a higher relative abundance of 4 bacterial species. Notably, low levels of , , and (EAS) in the saliva may be associated with the nonresponse of patients with OSCC to NAIT. A nomogram based on EAS was developed and validated to determine the efficacy of NAIT. The area under the curve for the training cohort was 0.81 (95% confidence interval, 0.66 to 0.81). Quantitative polymerase chain reaction confirmed that low levels of salivary EAS effectively identified nonresponders to NAIT. Furthermore, the low abundance of salivary EAS was closely correlated with a low density of intratumoral CD4, CD14, CD68, and FOXP3 cells. Metabolic functional annotation revealed numerous biosynthetic processes associated with EAS that were more active in responders. In summary, this study provides valuable data resources for the salivary microbiome and reveals that nonresponders have different salivary microbiome profiles than responders do before NAIT. Low salivary EAS levels can serve as potential biomarkers for distinguishing nonresponders from responders.
大多数被诊断为口腔鳞状细胞癌（OSCC）的患者表现为局部晚期，其预后通常较差。虽然免疫疗法为提高患者生存率提供了潜在的改善，但由于反应率低，其疗效受到限制。微生物组广泛参与肿瘤免疫，并可能在免疫疗法中发挥作用。本研究旨在探讨口腔（唾液）微生物组与接受新辅助免疫治疗（NAIT）的 OSCC 患者免疫治疗反应之间的潜在关联。对 47 名接受临床试验（NCT04649476）中 NAIT 的 OSCC 患者进行唾液宏基因组测序。根据病理反应将患者分为应答者和无应答者。结果表明，NAIT 前无应答者的唾液微生物组丰富度低于应答者。差异分析显示，无应答者的 34 种细菌的相对丰度较低，4 种细菌的相对丰度较高。值得注意的是，唾液中 、 、 和 （EAS）水平较低可能与 OSCC 患者对 NAIT 的无反应有关。基于 EAS 建立并验证了一个预测 NAIT 疗效的诺莫图。训练队列的曲线下面积为 0.81（95%置信区间，0.66 至 0.81）。定量聚合酶链反应证实，唾液中 EAS 水平低可有效识别对 NAIT 无反应的患者。此外，唾液中 EAS 的低丰度与肿瘤内 CD4、CD14、CD68 和 FOXP3 细胞密度低密切相关。代谢功能注释揭示了与 EAS 相关的许多生物合成过程，这些过程在应答者中更为活跃。总之，本研究为唾液微生物组提供了有价值的数据集，并揭示了无应答者在接受 NAIT 治疗前的唾液微生物组谱与应答者不同。低唾液 EAS 水平可作为区分应答者和无应答者的潜在生物标志物。
