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8094d30a-2a87-412f-941f-0205918d5dac - samples

ABSTRACT: We retrospectively collected 150 non-metastatic, pretreatment, formalin-fixed, paraffin-embedded (FFPE) nasopharyngeal carcinoma (NPC) samples as validation cohort 1. Also, we prospectively collected 32 FFPE samples from NPC patients enrolled in a trial evaluating anti-PD-1 antibody as validation cohort 2. Total RNA was extracted and hybridised to an Affymetrix HTA 2.0 microarray. In this study, we investigated the immune status of the tumour microenvironment (TME) based on gene expression profiles to classify NPC into biologically distinct immune subtypes, and clarify their associations with prognosis and immunotherapy response.

PROVIDER: EGAD00001006273 | EGA |

REPOSITORIES: EGA

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Project description:We retrospectively collected 150 non-metastatic, pretreatment, formalin-fixed, paraffin-embedded (FFPE) nasopharyngeal carcinoma (NPC) samples as validation cohort 1. Also, we prospectively collected 32 FFPE samples from NPC patients enrolled in a trial evaluating anti-PD-1 antibody as validation cohort 2. Total RNA was extracted and hybridised to an Affymetrix HTA 2.0 microarray. In this study, we investigated the immune status of the tumour microenvironment (TME) based on gene expression profiles to classify NPC into biologically distinct immune subtypes, and clarify their associations with prognosis and immunotherapy response.

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Tumors with neoadjuvant chemotherapy

Project description:Using whole genome mRNA expression profiling of primary human tumors and unsupervised hierarchical cluster analyses, 3 novel molecular subsets (basal, luminal and p53-like subsets) of muscle-invasive bladder cancer (MIBC) were identified. 23 MVAC treated samples were used for the validation of three MIBC subsets MVAC cohort consisted of 23 FFPE pretreatment tumors (TURs) from a Phase III clinical trial were used to validate 3 molecular subsets including basal, luminal and p53-like subsets We used Illumina cDNA-mediated Annealing, Selection, Extension, and Ligation (DASL) assay that is specifically designed for the gene expression of RNA that is extracted from FFPE.

2014-02-10 | E-GEOD-52219 | biostudies-arrayexpress

Single-cell transcriptomics reveals regulators underlying immune cell diversity and immune subtypes associated with prognosis in nasopharyngeal carcinoma

Project description:Nasopharyngeal carcinoma (NPC) is an aggressive malignancy with extremely skewed ethnic and geographic distributions. Increasing evidence indicates that targeting the tumour microenvironment (TME) represents a promising therapeutic approach in NPC, highlighting an urgent need to deepen the understanding of the complex NPC TME. Here, we generated single-cell transcriptome profiles for 7,581 malignant cells and 40,285 immune cells from 15 primary NPC tumours and one normal sample. We revealed malignant signatures capturing intratumoural transcriptional heterogeneity and predicting aggressiveness of malignant cells. Diverse immune cell subtypes were identified, including novel subtypes such as CLEC9A+ dendritic cells (DCs). We further revealed transcriptional regulators underlying immune cell diversity, and cell-cell interaction analyses highlighted promising immunotherapeutic targets in NPC. Moreover, we established the immune subtype-specific signatures, and demonstrated that the signatures of macrophages, plasmacytoid dendritic cells (pDCs), CLEC9A+ DCs, natural killer (NK) cells, and plasma cells were significantly associated with improved survival outcomes in NPC. Taken together, our findings represent a unique resource providing in-depth insights into the cellular heterogeneity of NPC TME and highlight potential biomarkers for anticancer treatment and risk stratification, laying a new foundation for the precision therapies in NPC.

2020-07-20 | GSE150430 | GEO

Tumour Heterogeneity and Intercellular Networks of Nasopharyngeal Carcinoma at Single Cell Resolution

Project description:The heterogeneous nature of tumour microenvironment (TME) underlying diverse treatment responses remains unclear in nasopharyngeal carcinoma (NPC). Here, we profile 176,447 cells from 10 NPC tumour-blood pairs, using single-cell transcriptome coupled with T cell receptor sequencing. Our analyses reveal 53 cell subtypes, including tumour-infiltrating CD8+ T, regulatory T (Treg), and dendritic cells (DCs), as well as malignant cells with different Epstein-Barr virus infection status. Trajectory analyses reveal exhausted CD8+ T and immune-suppressive TNFRSF4+ Treg cells in tumours might derive from peripheral CX3CR1+CD8+ T and naïve Treg cells, respectively. Moreover, we identify immune-regulatory and tolerogenic LAMP3+ DCs. Noteworthily, intensive inter-cell interactions are observed among LAMP3+ DCs, Treg, exhausted CD8+ T, and malignant cells, suggesting potential cross-talks to foster an immune-suppressive niche for the TME. Collectively, our study uncovers the heterogeneity and interacting molecules of the TME in NPC at single-cell resolution, which provide insights into the mechanisms underlying NPC progression and the development of precise therapies for NPC.

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Impact of immune repertoire in Muscle – Invasive Bladder Cancer (MIBC) on predicting response and survival after neoadjuvant cisplatin-based chemotherapy (NAC)

Project description:Purpose: Neoadjuvant cisplatin-based Chemotherapy (NAC) followed by cystectomy is the standard of care for patients with muscle-invasive bladder cancer (MIBC). Unfortunately, only a third of patients achieve pathologic complete response (pCR). The aim of this study is to deeply investigate the role played by peripheral immunogenicity and the Tumor and Immune Microenvironment (TIME) in patients undergoing NAC to identify predictive and pharmacodynamic biomarkers associated with treatment response or treatment resistance. Experimental design: N= 19 patients with MIBC received NAC and were classified as pCR (n=10) or non-pCR (n=9). Bulk RNA-seq was performed on 13 formalin-fixed paraffin-embedded (FFPE) tumor biopsies collected before treatment with NAC and immune protein evaluations using GeoMx Digital Spatial Profiling (DSP) technology were performed on matched FFPE tumor biopsies collected before and after treatment with NAC. Matching Peripheral blood collected prior treatment initiation and during cystectomy was assessed for lymphocytes and neutrophils counts. Kaplan–Meier analyses and Cox PH regression models were used for survival analyses (OS). Results: Genes associated with immune signaling and DNA repair signaling correlated with treatment outcome of patients with MIBC undergoing NAC. At baseline, gene expression analysis and digital special profile highlighted an abundance of B cells and a reduced neuroendocrine phenotype in the TME of pCR vs. no-pCR. Increased protein expression of immune checkpoints molecules (e.g. LAG3, ICOS, PD-L1) was also observed in the TME of patients with no-pCR. In peripheral blood, a significant increase of lymphocytes and decrease of neutrophils counts, respectively, was observed in pCR vs no-pCR following NAC. Conclusions: When confirmed on a larger cohort, our results might lead to novel therapeutic strategies and to novel biomarkers predicting patients likely to respond to NAC.

2024-08-16 | GSE247185 | GEO

The FFPE samples of the primary vs. recurrent glioblastoma validation cohort

Project description:The FFPE samples of the primary vs. recurrent glioblastoma validation cohort

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Single-cell RNA sequencing defines the interplay between tumor cells, virus and microenvironment in nasopharyngeal carcinoma

Project description:Purpose: While viruses play critival roles in many human malignancies, the influence of virus infection on the tumor microenviroment(TME) and how this impacts disease progression are poorly characterized. Methods: we applied both Smart-seq2 and 10X Genomics chemistry to ~104000 cells from 19 EBV+ NPC patients and 7 nonmalignant nasopharyngeal biopsies. Results: 1. We have defined the complex interplay between tumor cells, virus infection, and the TME at single-cell resolution. 2. An epithelial-immune dual feature of malignant cells was discovered and associated with poor prognosis. 3. Stromal and immune cells in the TME were remodeled by tumor cells and virus infection. 4. EBV gene expression was found to correlate with complement factor expression in malignant cells, which, in turn, mediated T cell modulation and recruitment. 5. We subtyped NPC patients into 5 groups with different prognoses according to their respective TME compositions. Conclusion: Our results provide new insights into the multicellular ecosystem of NPC and offer important clinical implications.

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