唾液微生物组与 OSCC 的新辅助免疫疗法反应有关

Journal of dental research Pub Date : 2024-09-01 Epub Date: 2024-08-05 DOI:10.1177/00220345241262759
X X Wang, Y T Liu, J G Ren, H M Liu, Q Fu, Y Yang, Q Y Fu, G Chen
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摘要

大多数确诊为口腔鳞状细胞癌(OSCC)的患者都是局部晚期,通常预后较差。虽然免疫疗法有可能提高患者的生存率,但其疗效却因反应率低而受到影响。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 OSCC 患者免疫治疗反应之间的潜在关联。在一项临床试验(NCT04649476)中,对47名接受新辅助免疫疗法(NAIT)的OSCC患者进行了唾液元基因组测序。根据病理反应将患者分为有反应者和无反应者。结果显示,在接受新辅助免疫疗法(NAIT)前,无应答者唾液微生物组的物种丰富度低于有应答者。差异分析显示,无反应者的 34 种细菌相对丰度较低,而 4 种细菌相对丰度较高。值得注意的是,唾液中Eubacterium infirmum、Actinobaculum和Selenomas(EAS)的低水平可能与OSCC患者对NAIT无反应有关。为了确定 NAIT 的疗效,我们开发并验证了基于 EAS 的提名图。训练队列的曲线下面积为 0.81(95% 置信区间为 0.66 至 0.81)。定量聚合酶链反应证实,唾液 EAS 含量低可有效识别对 NAIT 无应答者。此外,唾液EAS含量低与瘤内CD4+、CD14+、CD68+和FOXP3+细胞密度低密切相关。代谢功能注释揭示了许多与 EAS 相关的生物合成过程,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宝贵的数据资源,并揭示了非应答者与应答者在 NAIT 前的唾液微生物组特征不同。低唾液 EAS 水平可作为潜在的生物标志物,用于区分非应答者和应答者。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Salivary Microbiome Relates to Neoadjuvant Immunotherapy Response in OSCC.

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 Eubacterium infirmum, Actinobaculum, and Selenomas (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.

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