Department of Hematology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.
Department of Lymphoma, Cancer Hospital of University of Chinese Academy of Sciences, Hangzhou, China.
Front Immunol. 2023 May 9;14:1146861. doi: 10.3389/fimmu.2023.1146861. eCollection 2023.
BACKGROUND/PURPOSE: It has been demonstrated that gut microbes are closely associated with the pathogenesis of lymphoma, but the gut microbe landscape and its association with immune cells in diffuse large B-cell lymphoma (DLBCL) remain largely unknown. In this study, we explored the associations between gut microbiota, clinical features and peripheral blood immune cell subtypes in DLBCL.
A total of 87 newly diagnosed DLBCL adults were enrolled in this study. The peripheral blood samples were collected from all patients and then submitted to immune cell subtyping using full-spectral flow cytometry. Metagenomic sequencing was applied to assess the microbiota landscape of 69 of 87 newly diagnosed DLBCL patients. The microbiotas and peripheral blood immune cell subsets with significant differences between different National Comprehensive Center Network-International Prognostic Indexes (NCCN-IPIs) (low-risk, low-intermediate-risk, intermediate-high-risk, high-risk) groups were screened.
A total of 10 bacterial phyla, 31 orders and 455 bacteria species were identified in 69 patients with newly diagnosed DLBCL. The abundances of 6 bacteria, including sp., sp., , , and were significantly different between the low-risk, low-intermediate-risk, intermediate-high-risk and high-risk groups, among which and were markedly accumulated in the high-risk group. The different bacteria species were mostly enriched in the Pyridoxal 5'-phosphate biosynthesis I pathway. In addition, we found that 2 of the 6 bacteria showed close associations with the different immune cell subtypes which were also identified from different NCCN-IPIs. In detail, the abundance of was negatively correlated with Treg cells, CD38+ nonrescue exhausted T cells, nature killer 3 cells and CD38+CD8+ effector memory T cells, while the abundance of was negatively correlated with HLA-DR+ NK cells, CD4+ Treg cells, HLA-DR+ NKT cells and HLA-DR+CD94+CD159c+ NKT cells.
This study first reveals the gut microbiota landscape of patients with newly diagnosed DLBCL and highlights the association between the gut microbiota and immunity, which may provide a new idea for the prognosis assessment and treatment of DLBCL.
背景/目的：已有研究表明，肠道微生物与淋巴瘤的发病机制密切相关，但弥漫性大 B 细胞淋巴瘤（DLBCL）的肠道微生物群及其与免疫细胞的关联在很大程度上尚不清楚。本研究旨在探讨 DLBCL 患者肠道微生物群与临床特征及外周血免疫细胞亚群的相关性。
本研究共纳入 87 例新诊断的 DLBCL 成人患者。采集所有患者的外周血样本，采用全谱流式细胞术进行免疫细胞亚群分型。应用宏基因组测序技术分析 69 例新诊断 DLBCL 患者的肠道微生物群。筛选不同 NCCN-IPI（低危、低中危、中高危、高危）组间肠道微生物群和外周血免疫细胞亚群存在显著差异的患者。
在 69 例新诊断的 DLBCL 患者中，共鉴定出 10 个细菌门、31 个目和 455 个细菌种。 、 、 、 、 等 6 种细菌的丰度在低危、低中危、中高危和高危组间存在显著差异，其中 和 在高危组中明显富集。不同的细菌种主要富集在吡哆醛 5'-磷酸生物合成 I 途径中。此外，我们发现这 6 种细菌中的 2 种与不同 NCCN-IPI 鉴定的不同免疫细胞亚群密切相关。具体而言， 的丰度与 Treg 细胞、CD38+非拯救耗竭性 T 细胞、自然杀伤细胞 3 细胞和 CD38+CD8+效应记忆 T 细胞呈负相关，而 的丰度与 HLA-DR+NK 细胞、CD4+Treg 细胞、HLA-DR+NKT 细胞和 HLA-DR+CD94+CD159c+NKT 细胞呈负相关。
本研究首次揭示了新诊断 DLBCL 患者的肠道微生物群景观，并强调了肠道微生物群与免疫之间的关联，这可能为 DLBCL 的预后评估和治疗提供新的思路。
