RNA-sequencing of gastric tissues derived from five inflamed-type and five desert-type tumors
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE289066 | GEO | 2025/02/18
REPOSITORIES: GEO
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Project description:Transforming gastric tumors from immunosuppressive to immunostimulatory is a potential approach to enhance immune checkpoint blockade response. Here, we developed a chromosomal instability subtype gastric cancer mouse model with an immunoactive tumor microenvironment (TME) and a stem cell-originated mouse-derived allograft model with an immunosuppressed TME to investigate mechanisms regulating the tumor immunophenotype and uncover therapeutic strategies to remodel the TME.
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Project description:BackgroundRecently, researches have begun to investigate the microbial communities associated with halophytes. Both rhizobacterial community composition and the environmental drivers of community assembly have been addressed. However, few studies have explored the structure of rhizobacterial communities associated with halophytic plants that are co-occurring in arid, salinized areas.MethodsFive halophytes were selected for study: these co-occurred in saline soils in the Ebinur Lake Nature Reserve, located at the western margin of the Gurbantunggut Desert of Northwestern China. Halophyte-associated bacterial communities were sampled, and the bacterial 16S rDNA V3-V4 region amplified and sequenced using the Illumina Miseq platform. The bacterial community diversity and structure were compared between the rhizosphere and bulk soils, as well as among the rhizosphere samples. The effects of plant species identity and soil properties on the bacterial communities were also analyzed.ResultsSignificant differences were observed between the rhizosphere and bulk soil bacterial communities. Diversity was higher in the rhizosphere than in the bulk soils. Abundant taxonomic groups (from phylum to genus) in the rhizosphere were much more diverse than in bulk soils. Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes and Planctomycetes were the most abundant phyla in the rhizosphere, while Proteobacteria and Firmicutes were common in bulk soils. Overall, the bacterial community composition were not significantly differentiated between the bulk soils of the five plants, but community diversity and structure differed significantly in the rhizosphere. The diversity of Halostachys caspica, Halocnemum strobilaceum and Kalidium foliatum associated bacterial communities was lower than that of Limonium gmelinii and Lycium ruthenicum communities. Furthermore, the composition of the bacterial communities of Halostachys caspica and Halocnemum strobilaceum was very different from those of Limonium gmelinii and Lycium ruthenicum. The diversity and community structure were influenced by soil EC, pH and nutrient content (TOC, SOM, TON and AP); of these, the effects of EC on bacterial community composition were less important than those of soil nutrients.DiscussionHalophytic plant species played an important role in shaping associated rhizosphere bacterial communities. When salinity levels were constant, soil nutrients emerged as key factors structuring bacterial communities, while EC played only a minor role. Pairwise differences among the rhizobacterial communities associated with different plant species were not significant, despite some evidence of differentiation. Further studies involving more halophyte species, and individuals per species, are necessary to elucidate plant species identity effects on the rhizosphere for co-occurring halophytes.
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Project description:The invasive potential of gastric cancers (GCs) defines the hallmarks of malignancies; however, the cellular components and their molecular features associated with tumor invasiveness in GC microenvironments (TME) are poorly understood. In this study, we constructed a comprehensive atlas of 23,060 single cells obtained from surgically dissected superficial and deep layers of five diffuse-type GC along with matched normal. As a result, seven major cell types were identified. Fibroblasts, endothelial cells, and myeloid cells were categorized as being enriched in the deep layers. Cell type-specific clustering further revealed that the superficial-to-deep layer transition is associated with enrichment in inflammatory endothelial cells and fibroblasts with upregulated CCL2 transcripts. This study reveals the spatial reprogramming of the TME that may underlie invasive tumor potential in diffuse-type GC. This TME profiling across tumor layers suggests new targets, such as CCL2, that can modify the TME to inhibit tumor progression in diffuse-type GC.
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2021-07-29 | GSE180887 | GEO
Project description:Recently neoadjuvant therapy (NAT) is being increasingly used in the treatment of pancreatic ductal adenocarcinoma (PDAC). However, how NAT differentially impacts the tumor and the tumor microenvironment (TME) is still poorly defined. Therefore, we compared the spatial transcriptomics profiles in tumor and the TME of PDACs resected from patients with versus without NAT. We found that NAT can significantly upregulate multiple key complement genes (C3, C1S, C1R, C4B and C7) in TME but not in tumor, making the complement pathway the most significantly modified pathways by NAT. In addition, the NAT-treated patients s with higher TME complement show significantly higher expression of gene signatures for immunomodulatory and neurotropic fibroblast, mast cells, CD4+ T cells and monocytes, significantly lower expression of immune exhaustion gene signature, and improved overall survival. Our results suggested that NAT may have immunostimulatory effect for PDAC through upregulating TME complement signaling.
2024-06-05 | GSE240078 | GEO
Project description:Background Thyroid cancer (THCA) is the most prevalent malignant disease of the endocrine system, in which 5-year survival can attain about 95%, but patients with metastasis have a poor prognosis. Very little is known about the role of CAPN8 in the metastasis of THCA. In particular, the effect of CAPN8 on the tumor immune microenvironment (TIME) and immunotherapy response is unclear. Material and methods Multiome datasets and multiple cohorts were acquired for analysis. Firstly, the expression and the prognostic value of CAPN8 were explored in public datasets and in vitro tumor tissues. Then, hierarchical clustering analysis was performed to identify the immune subtypes of THCA according to the expression of CAPN8 and the activities of related pathways. Subsequent analyses explored the different patterns of TIME, genetic alteration, DNA replication stress, drug sensitivity, and immunotherapy response among the three immune phenotypes. Finally, five individual cohorts of thyroid cancer were utilized to test the robustness and extrapolation of the three immune clusters. Results CAPN8 was found to be a significant risk factor for THCA with a markedly elevated level of mRNA and protein in tumor tissues. This potential oncogene could induce the activation of epithelial–mesenchymal transition and E2F-targeted pathways. Three subtypes were identified for THCA, including immune exhausted, inflamed, and immune desert phenotypes. The exhausted type was characterized by a markedly increased expression of inhibitory receptors and infiltration of immune cells but was much more likely to respond to immunotherapy. The immune desert type was resistant to common chemotherapeutics with extensive genomic mutation and copy number variance. Conclusion The present study firstly explored the role of CAPN8 in the metastasis of THCA from the aspects of TIME. Three immune subtypes were identified with quite different patterns of prognosis, immunotherapy response, and drug sensitivity, providing novel insights for the treatment of THCA and helping understand the cross-talk between CAPN8 and tumor immune microenvironment.
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Project description:EGFR Is a Master Switch Between Immunosuppressive and Immunoactive Tumor Microenvironment in Inflammatory Breast Cancer
2023-01-11 | GSE190559 | GEO
Project description:Gastric cancer is the 3rd most lethal cancer worldwide, and the genomic status of its cancer cells has not translated into effective prognostic or therapeutic strategies. We therefore hypothesize that outcomes may depend on the tumor microenvironment (TME), and in particular cancer-associated fibroblasts (CAFs). However, very little is known about the role of CAFs in gastric cancer. To address this, we map the transcriptional landscape of human gastric cancer stroma by microdissection and RNA sequencing of CAFs from gastric cancer patients. We find a stromal gene signature associated with poor disease outcome. This signature is regulated by the transcription factor Heat Shock Factor 1 (HSF1), that activates CAF-derived extracellular vesicles (EVs) that transfer components including Inhibin Subunit Beta A (INHBA) and Thrombospondin 2 (THBS2), to the TME to promote cancer. Together, our work provides the first transcriptional map of human gastric cancer stroma, and highlights HSF1 and its transcriptional targets as potential diagnostic and therapeutic targets in the genomically stable tumor microenvironment.
2021-02-28 | GSE165211 | GEO