Similar Datasets
Project description:We analyzed 40,799 single cells from nine samples and found that in EGFR-mutant LUAD, tumor cells generated an immunosuppressive microenvironment by releasing cytokines to attract suppressive immune cells such as myeloid-derived suppressor cells (MDSCs) directly or indirectly by interacting with macrophages, dendritic cells, or other cell types. By contrast, EGFR wild-type LUAD had a greater ability to recruit immunocompetent T cells such as TRMs and Th1 cells, thus driving a proinflammatory microenvironment.
2022-02-09 | GSE171145 | GEO
Project description:Abstract from manuscript Glioblastoma develops an immunosuppressive microenvironment that fosters tumorigenesis and resistance to current therapeutic strategies. Here we use multiplexed tissue imaging and single-cell RNA-sequencing to characterize the composition, spatial organization, and clinical significance of extracellular purinergic signaling in glioblastoma. We show that glioblastoma exhibit strong expression of CD39 and CD73 ectoenzymes, correlating with increased adenosine levels. Microglia are the predominant source of CD39, while CD73 is principally expressed by tumor cells, particularly in tumors with amplification of EGFR and astrocyte-like differentiation. Spatially-resolved single-cell analyses demonstrate strong spatial correlation between tumor CD73 and microglial CD39, and that their spatial proximity is associated with poor clinical outcomes. Together, this data reveals that tumor CD73 expression correlates with tumor genotype, lineage differentiation, and functional states, and that core purine regulatory enzymes expressed by neoplastic and tumor-associated myeloid cells interact to promote a distinctive adenosine-rich signaling niche and immunosuppressive microenvironment potentially amenable to therapeutic targeting.
2022-06-27 | ST002203 | MetabolomicsWorkbench
Project description:The Dual Erb B Inhibition in Oesophago-gastric Cancer (DEBIOC) trial reported an acceptable safety profile for neoadjuvant Oxaliplatin and Capecitabine (Xelox) +/- AZD8931 in oesophageal adenocarcinoma (OAC) but limited efficacy. We evaluated the impact of neoadjuvant Xelox +/-AZD8931 on biological pathways using a unique software-driven solution. Transcriptomic profiles from 25 pre-treatment FFPE OAC biopsies and 17 matched resection specimens, treated with Xelox+AZD8931 (n=16) and Xelox alone (n=9), were analysed using the Almac claraT total mRNA report. Tumour Infiltrating Lymphocytes (TILs) were assessed digitally using QuPath software. Hierarchical clustering identified three molecular subgroups classified by activation of innate immune signalling. The Immune High subgroup was associated with HER2 positivity, increased pathological response and a marked reduction in immune signalling and TILs following neoadjuvant therapy. The Immune Low cluster was pre-dominantly HER2/EGFR negative and EGFR positivity was associated with the Immune Mixed subgroup. Neoadjuvant therapy induced angiogenesis and EMT signalling and a reduction in DNA repair signatures with AZD8931 also promoting an immunosuppressive microenvironment. OAC may be subdivided into three immune-related subgroups which undergo modulation in response to neoadjuvant therapy with marked suppression of the immune microenvironment in HER2 positive/Immune High tumours.
2024-09-01 | E-MTAB-13741 | biostudies-arrayexpress
Project description:Single Cell sequencing analysis of Inflammatory Breast Cancer Samples
| PRJNA787545 | ENA
Project description:Re-education of immune cells in tumor microenvironment is required for optimal treatment outcome. The prevailing notion is that B cells, a major immune cell type in tumors, are immunosuppressive and pro-tumoral. However, why B cells inhibit tumor progression in certain contexts remains unexplained. By single cell dissection of B cell heterogeneity in longitudinal samples of breast cancer patients before and after neoadjuvant chemotherapy, we revealed a distinct subset of B cells emerges after chemotherapy, which is predictive for therapeutic efficacy and prognosis in multiple patient cohorts. Using three immunocompetent mouse models, our in vivo experiments faithfully recapitulated the subset switch of human tumor-infiltrating B cells during chemotherapy. Employing B-specific deletion and adoptive transfer experiment, we showed that ICOSL in this B cell subset boosts anti-tumor immunity by enhancing the ratio of effector and regulatory T cells. The signature of ICOSL+ B cell subset is imprinted by complement-CR2 signaling, which is triggered by chemotherapy-induced immunogenic tumor cell death. Moreover, by screening the cell line encyclopedia, we identified CD55, a complement inhibitory protein, determines the dual roles of B cells in the response of various malignancies to chemotherapy. Collectively, our study demonstrates a critical role of B cell subset switch in chemotherapy response and have implications for designing novel therapeutic approaches.
2020-03-13 | GSE135710 | GEO
Project description:Chronic inflammation promotes breast tumor growth and invasion by accelerating angiogenesis and tissue remodeling in the tumor microenvironment. The relationship between inflammation and estrogen, which drives the growth of 70 percent of breast tumors, is complex. Low levels of estrogen exposure stimulate macrophages and other inflammatory cell populations, but very high levels are immune suppressive. Breast tumor incidence is increased by obesity and age, which interact to influence inflammatory cell populations in normal breast tissue. The molecular impact of these factors on tumor initiation and growth is not well-understood. We modeled the difference in gene expression between 195 breast adenocarcinomas and 195 matched adjacent normal breast tissue samples, using age, body mass index (BMI), and tumor subtype as covariates. Age and BMI were independently associated with inflammation in normal tissue but not tumors. Older patients with ER-positive disease had tumors with higher levels of Estrogen Receptor (ER) signaling compared to adjacent normal tissue and had lower relative levels of tumor macrophage expression. We developed a novel statistic to quantify the rewiring of gene co-expression networks and demonstrate that in ER-positive tumors basal gene networks are rewired even though their expression levels of these genes are not significantly different from those in adjacent normal tissue. Patient age influences the molecular profile of ER-positive breast tumors. Our data support an immunosuppressive effect of estrogen signaling in the breast tumor microenvironment, suggesting this effect contributes to the greater presence of prognostic and therapeutically relevant immune cells in ER-negative tumors. 137 total samples: 43 mammaplastic reduction, 47 breast adenocarcinoma, 47 paired adjacent normal breast tissue
2016-07-01 | E-GEOD-70905 | biostudies-arrayexpress
Project description:Chronic inflammation promotes breast tumor growth and invasion by accelerating angiogenesis and tissue remodeling in the tumor microenvironment. The relationship between inflammation and estrogen, which drives the growth of 70 percent of breast tumors, is complex. Low levels of estrogen exposure stimulate macrophages and other inflammatory cell populations, but very high levels are immune suppressive. Breast tumor incidence is increased by obesity and age, which interact to influence inflammatory cell populations in normal breast tissue. The molecular impact of these factors on tumor initiation and growth is not well-understood. We modeled the difference in gene expression between 195 breast adenocarcinomas and 195 matched adjacent normal breast tissue samples, using age, body mass index (BMI), and tumor subtype as covariates. Age and BMI were independently associated with inflammation in normal tissue but not tumors. Older patients with ER-positive disease had tumors with higher levels of Estrogen Receptor (ER) signaling compared to adjacent normal tissue and had lower relative levels of tumor macrophage expression. We developed a novel statistic to quantify the rewiring of gene co-expression networks and demonstrate that in ER-positive tumors basal gene networks are rewired even though their expression levels of these genes are not significantly different from those in adjacent normal tissue. Patient age influences the molecular profile of ER-positive breast tumors. Our data support an immunosuppressive effect of estrogen signaling in the breast tumor microenvironment, suggesting this effect contributes to the greater presence of prognostic and therapeutically relevant immune cells in ER-negative tumors. 296 total samples: 148 breast adenocarcinoma, 148 paired adjacent normal breast tissue
2016-07-01 | E-GEOD-70947 | biostudies-arrayexpress
Project description:Fresh human breast tumor tissue was dissociated into single cells and viably frozen. Patient samples were annotated as having an ""exhausted"" or ""non-exhausted"" immune environment based on CyTOF characterization of T cell phenotypes (Wagner et al, Cell 2019). 14 samples (7 exhausted, 7 non-exhausted) were selected for scRNA-seq (without prior cell type enrichment) with the goal to compare the two immune environment types and to comprehensively characterize exhaustion-associated features of the tumor microenvironment.
2023-08-25 | E-MTAB-10607 | biostudies-arrayexpress
Project description:Epidermal growth factor receptor-targeted chimeric antigen receptor T cell (EGFR CAR-T) is potent and specific in suppressing triple-negative breast cancer (TNBC) cell growth in vitro and in vivo. However, a subset of mice soon acquired resistance, which limits the potential use of EGFR CAR-T. The aim of this study is to find a way to overcome the observed resistance. Transcriptomic analysis results revealed that EGFR CAR-T treatment led to the induction of a cohort of immunosuppressive genes, presumably through Interferon gamma (IFNγ signaling, in EGFR CAR-T-resistant TNBC tumors. EGFR CAR-T-induced immunosuppressive genes were found to be associated with EGFR CAR-T-activated enhancers and especially sensitive to THZ1, a CDK7 inhibitor, out of a panel of small molecules targeting epigenetic modulators screened. Accordingly, combination therapy of THZ1 and EGFR CAR-T suppressed immune resistance and tumor growth and metastasis in TNBC tumor models including human MDA-MB-231 cells-derived xenografts, TNBC patient-derived xenografts, and mouse EMT6 cells-derived allografts in mice. Taken together, we demonstrated that CAR-T therapy-induced immune resistance can be overcome by transcriptional modulation using epigenetic inhibitors, providing a therapeutic avenue for treating TNBC in the clinic.
2021-05-20 | GSE164902 | GEO
Project description:EGFR-inhibition is required for targeted therapies of ERBB2-positive/EGFR high breast cancer. Approximately 30% of human ERBB2-positive breast tumors also express EGFR.
2014-08-13 | GSE50107 | GEO