PD-GER
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB17777 | ENA |
REPOSITORIES: ENA
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Project description:Growing evidence supports the gut microbiota as a promising target for enhancing the efficacy of cancer immunotherapy. However, the success of microbiota-targeting interventions has been limited, partly due to interindividual microbial heterogeneity. Here, we designed and constructed a defined consortium (RCom) of 15 bacterial species that are associated with improved clinic response to anti-PD-1 treatment and were mostly isolated from the feces of responder patients. Through in silico prediction and experimental characterization in vitro and in vivo, we demonstrated that the RCom is a relatively cooperative community, in which five Bacteroidetes species and ten Firmicutes species act together to establish optimal engraftment and produce immunomodulatory metabolites. Despite a profound heterogeneity of the baseline gut microbiota, oral supplementation of the RCom consistently improved the anti-tumor activity of anti-PD-1 by increasing intratumoral infiltration and cytotoxic activity of CD8+ T cells in syngeneic tumor models. Moreover, administration of the RCom circumvented the anti-PD-1 resistance in mice conferred by fecal microbiota transplantation from individual non-responsive patients. The RCom is thus a potential adjuvant to augment responsiveness to anti-PD-1 therapy in cancer
2026-01-14 | PXD064618 | Pride
Project description:We performed a phase I clinical trial to assess the safety and feasibility of fecal microbiota transplantation (FMT) and re-induction of anti-PD-1 immunotherapy in patients with anti-PD-1-refractory metastatic melanoma. FMT donors were two metastatic melanoma patients who achieved a durable complete response. FMT recipient patients were metastatic melanoma patients who failed at least one anti-PD-1 line of treatment. Each recipient patient received FMT implants from only one of the two donors. FMT was conducted by both colonoscopy and oral ingestion of stool capsules, followed by anti-PD-1 re-treatment (Nivolumab, BMS). Recipient patients underwent pre- and post-treatment stool sampling, tissue biopsy of both gut and tumor, and total body imaging. Clinical responses were observed in three patients, including two partial responses and one complete response. Notably, treatment with FMT was associated with favorable changes in immune cell infiltrates and gene expression profiles in both the gut lamina propria and the tumor microenvironment.
2020-12-31 | GSE162436 | GEO
Project description:The deleterious impact of antibiotics (ATB) on the microbiome negatively impacts immune checkpoint inhibitor (ICI) response. We assessed the efficacy of DAV132, a colon-targeted adsorbent in 70 healthy volunteers (HV) randomized to receive ceftazidime-avibactam or piperacillin-tazobactam alone or in combination with oral administration of DAV132. DAV132 significantly decreased fecal but not plasma ATB concentration. When coadministered with either ATB, DAV132 prevented loss of microbiome diversity and induced rapid recovery of the baseline microbiota composition. Moreover, bacterial probe set qPCR-based assay confirmed metagenomics results that DAV132 preserved several commensals such as Alistipes shahii, Blautia obeum and Faecalibacterium praunsnitzii. Fecal microbiota transplantation in murine tumor models from HV treated with ATB alone reduced antitumor responses to anti-PD-1, while transplanted samples from HV treated with ATB+DAV132 circumvented resistance to anti-PD-1. This anti-tumor response in mice was associated with tumor microenvironment increased the ratio of total CD8+ T cells/ regulatory T cells, and three distinct activated CD8+ T cell population whiting the tumor within the tumor, as well as gene expression of interferon gamma (INFγ) in the mesenteric lymph nodes. In addition, a unique gene signature with downregulation of IL-6 and reactive oxygen pathways was found in the mice treated with FMT from ATB+DAV132 sample and treated with anti-PD-1. DAV132 represents a new strategy for overcoming ATB-related dysbiosis and further studies are warranted to evaluate its efficacy in cancer patients on ICI.
2024-08-12 | GSE251922 | GEO
Project description:Neovascular age-related macular degeneration (nAMD) remains a major cause of visual impairment and puts considerable burden on patients and health care systems. L-DOPA-treated Parkinson Disease (PD) patients have been shown to be partially protected from nAMD, but the mechanism remains unknown. Using murine models combining 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD and laser-induced nAMD, standard PD treatment of L-DOPA/DOPA-decarboxylase inhibitor, or specific dopamine receptor inhibitors, we here demonstrate that L-DOPA treatment-induced increase of dopamine receptor D2 (DRD2) signaling inhibits choroidal neovascularization independently of MPTP-associated nigrostriatal pathway lesion. Analyzing a retrospective cohort of more than two hundred thousand nAMD patients receiving anti-VEGF treatment from the French nationwide insurance database, we show that DRD2-agonist treated (PD) patients have a significantly delayed age of onset for nAMD (81.4 (±7.0) vs 79.4 (±8.1) years old, respectively, p<0.0001) and reduced need for anti-VEGF therapies (-0.6 injections per 100 mg/day daily dose of DRD2 agonists the second year of treatment), similar to the L-DOPA treatment. While providing a mechanistic explanation for an intriguing epidemiological observation, our findings suggest that systemic DRD2 agonists might constitute an adjuvant therapy to delay and reduce the need for anti-VEGF therapy in nAMD patients.
2024-09-13 | GSE266525 | GEO
Project description:This study aimed to analyze changes in gut microbiota composition in mice after transplantation of fecal microbiota (FMT, N = 6) from the feces of NSCLC patients by analyzing fecal content using 16S rRNA sequencing, 10 days after transplantation. Specific-pathogen-free (SPF) mice were used for each experiments (N=4) as controls.
2023-07-01 | E-MTAB-12812 | biostudies-arrayexpress
Project description:This phase II trial studies the effect of fecal microbiota transplant and re-introduction of anti-PD-1 therapy (pembrolizumab or nivolumab) in treating anti-PD-1 non-responders with colorectal cancer that has spread to other places in the body (metastatic). Fecal microbiota transplants contain the normal bacteria and viruses found in fecal (stool) material. Immunotherapy with monoclonal antibodies, such as pembrolizumab and nivolumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving pembrolizumab or nivolumab with fecal microbiota transplants may help to control the disease.
| 2365430 | ecrin-mdr-crc
Project description:Fecal Microbiota rawdata from autistic model mice. Female and Male Poly I:C treated mice were compared at microbiota level.
2023-05-04 | E-MTAB-11150 | biostudies-arrayexpress
Project description:Parkinson's disease (PD) is a common neurodegenerative disease in middle-aged and elderly people. The disorder of gut microbiota is involved in the pathophysiological process of various neurological diseases, and many studies have confirmed that gut microbiota is involved in the progression of PD. As one of the most effective methods to reconstruct gut microbiota, fecal microbiota transplantation (FMT) has been considered as an important treatment for PD. However, the mechanism of FMT treatment for PD is still lacking, which requires further exploration and can facilitate the application of FMT. As a model organism, Drosophila is highly conserved with mammalian system in maintaining intestinal homeostasis. In this study, there were significant differences in the gut microbiota of conventional Drosophila colonized from PD patients compared to those transplanted from normal controls. And we constructed rotenone-induced PD model in Drosophila followed by FMT in different groups, and investigated the impact of gut microbiome on transcriptome of the PD host. Microbial analysis by 16S rDNA sequencing showed that gut microbiota could affect bacterial structure of PD, which was confirmed by bacterial colonization results. In addition, transcriptome data suggested that gut microbiota can influence gene expression pattern of PD. Further experimental validations confirmed that lysosome and neuroactive ligand-receptor interaction are the most significantly influenced functional pathways by PD-derived gut microbiota. In summary, our data reveals the influence of PD-derived gut microbiota on host transcriptome and helps better understanding the interaction between gut microbiota and PD through gut-brain axis. The present study will facilitate the understanding of the mechanism underlying PD treatment with FMT in clinical practice.
2023-01-13 | GSE221760 | GEO