Integration analysis of tumor metagenome and peripheral immunity data of diffuse large-B cell lymphoma

Abstract

Background/purposeIt 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.MethodA 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.ResultsA 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 Blautia sp.CAG 257, Actinomyces sp.S6 Spd3, Streptococcus parasanguinis, Bacteroides salyersiae, Enterococcus faecalls and Streptococcus salivarius were significantly different between the low-risk, low-intermediate-risk, intermediate-high-risk and high-risk groups, among which Streptococcus parasanguinis and Streptococcus salivarius 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 Bacteroides salyersiae 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 Streptococcus parasanguinis was negatively correlated with HLA-DR+ NK cells, CD4+ Treg cells, HLA-DR+ NKT cells and HLA-DR+CD94+CD159c+ NKT cells.ConclusionThis 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.

Characterizations of multi-kingdom gut microbiota in immune checkpoint inhibitor-treated hepatocellular carcinoma

“…Actinomyces were enriched in non-responders to advanced melanoma treated with immunotherapy, a non-response-associated module that linked Actinomyces to butyric acid (and derivatives) and cyclohexanecarboxylic acid ethyl ester, as well as to higher levels of neutrophils. 35 Actinomyces is more abundant in the high-risk group with diffuse large B-cell lymphoma 36 and lung cancer. 37 The presence of Senegalimassilia , which was detected almost exclusively in the NDB group in the current study (25% in NDB and 4% in DCB), may have a poorer prognosis, and a larger cohort is needed to confirm its feasibility and stability.…”

Exploring the Causal Relationship between Gut Bacteria and DLBCL through Comprehensive Integration of Prior Studies

“…Seok Jin Kim and co-authors reviewed the baseline gut microbiota of 189 newly diagnosed DLBCL patients, once again nding that the Bacteroidetes phylum dominated DLBCL, and the Enterobacteriaceae family was part of the dominant microbiota [14]. However, another study discovered signi cant differences in the abundance of six bacteria, including Streptococcus and Bacteroides, among DLBCL patients at baseline in different NCCN-IPI score groups [15]. Research also demonstrated that the phylum Proteobacteria signi cantly decreased in patients with primary gastrointestinal B-cell lymphoma, while microbiota lacking Proteobacteria interacted synergistically with the tumor necrosis factor (TNF) signaling pathway through lipopolysaccharides (LPS) and reinforced the NF-κB pathway through the MYD88-TLR4 signaling pathway, inducing the survival and malignant proliferation of intestinal B cells [16].…”

“…First, after excluding bacterial traits with unknown names from the MiBioGen dataset, 196 bacterial traits were retained, including nine phyla, 16 classes, 20 orders, 32 families, and 119 genera. Subsequently, to better identify gut microbial species closely associated with DLBCL as IVs, we conducted a review of relevant real-world observational studies, literature, and conference abstracts in PubMed and Google Scholar to compile a list of gut bacteria potentially related to DLBCL risk [12,13,[15][16][17][24][25][26][27][28]. The information of bacterial groups reported in the literature can be viewed in Table S2 and Table S3.…”