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Single-cell Sequencing Analysis Identifies Intratumoral Immune Cell Population in Head and Neck Squamous Cell Carcinoma from 4NQO-induced Mice upon JQ1 treatment

ABSTRACT: Single-cell Sequencing Analysis Identifies Intratumoral Immune Cell Population in Head and Neck Squamous Cell Carcinoma from 4NQO-induced Mice upon JQ1 treatment

PROVIDER: PRJNA855937 | ENA |

REPOSITORIES: ENA

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Single-cell Sequencing Analysis Identifies Intratumoral Cell Population in Head and Neck Squamous Cell Carcinoma from 4NQO-induced Mice upon anti-CD276 Therapy

Project description:In this study, we aimed to identifies the landscape alterations of intratumoral cell population in HNSCC from 4NQO-induced mice upon anti-CD276 treatment by using single cell sequencing analysis.we characterized the alterations of intratumoral cell population by separating cancer cells and yielded 6 distinct cancer cell subpopulations defined by the transcriptional state of cells and known marker genes, including the sunpopulation with pEMT, stress, typical epithelial differentiation, high cell-cycling, metabolism and immune fetures. In response of CD276 treatment, the frequecey of cells with pEMT, cell cycling and immune features are dcreased as compared to the vehicle control mice.

2021-05-28 | GSE164817 | GEO

Therapeutic targeting of BRD4 in head neck squamous cell carcinoma

Project description:The bromodomain and extraterminal family members are epigenetic readers and transcriptional coactivators which are critically involved in various biological processes including tumorigenesis. BRD4 has been increasingly appreciated as a key oncogene and promising anticancer target. Here, we sought to characterize the expression of BRD4 and its tumorigenic roles as well as therapeutic targeting in HNSCC. Expression of BRD4 mRNA and protein was determined by bioinformatics interrogation of public available databases, primary HNSCC samples and 4NQO-induced HNSCC animal model. The tumorigenic roles of BRD4 in HNSCC were evaluated by genetic and pharmacological approach in vitro and in vivo. Therapeutic efficiency of BRD4 targeting by JQ1 was assessed in three preclinical models including xenograft model, 4NQO-induced model and patients-derived xenograft model. Gene candidates responsible for therapeutic effects of JQ1 were identified by transcriptional profiling in HNSCC cells after JQ1 exposure. Significant upregulation of BRD4 was found in primary HNSCC samples and 4NQO-induced HNSCC model. Its overexpression associated with aggressive clinicopathological features and inferior overall and disease-free survival. BRD4 depletion by genetic silencing or pharmacological inhibition impaired cell proliferation, migration and invasion and reduced tumor growth and metastasis in vivo. Transcriptional profiling of HNSCC cells following JQ1 exposure identified hundreds of genes which might mediated its antitumor effects and enriched in cancer-relevant pathways. A novel prognostic risk score derived from JQ1-regualted genes was developed to stratify patients into subgroups with favorable or inferior prognosis. Our findings reveal that BRD4 serves as a novel oncogene driving cancer progression and a robust prognostic biomarker in HNSCC. Therapeutic targeting of BRD4 represents a potent and promising strategy against HNSCC.

2019-05-09 | GSE122522 | GEO

Single-cell Sequencing Analysis Identifies Intratumoral Cell Population in Head and Neck Squamous Cell Carcinoma from 4NQO-induced Mice upon anti-CD276 Therapy

Project description:Single-cell Sequencing Analysis Identifies Intratumoral Cell Population in Head and Neck Squamous Cell Carcinoma from 4NQO-induced Mice upon anti-CD276 Therapy

| PRJNA692131 | ENA

PIK3CA and p53 mutations promote 4NQO-initated head and neck tumor progression and metastasis in mice

Project description:The effect of gain of function mutations in p53, pik3ca, and both genes in mouse tongue subject to 4NQO treatment on gene expression is characterized by RNASeq.

2022-04-19 | GSE143716 | GEO

4NQO treatment may modulate gene expression in mouse tongue

Project description:Determine whether 4NQO treatment may modulate gene expression in mouse tongue. C57BL/6J mice were given 4NQO (100ug/ml in drink) for 8 weeks; Non-treated control samples were used for comparison.

2016-05-24 | GSE75374 | GEO

Transcriptomes Analysis of 4NQO induced-esophageal tumors of Wild Type and S100A14 CKO mice

Project description:Purpose: To fully realize the potential molecular mechanism that S100A14 deficiency enhances esophageal carcinogenesis Methods: Total RNA of esophageal tumors in 4NQO WT and 4NQO S100A 14 CKO group mice was extracted with TRIzol Reagent. RNA libraries were constructed using an Illumina TruSeq RNA Sample Preparation kit according to the manufacturer’s protocol. A total of 150 base paired-end reads were sequenced using the Novaseq 6000 S4 platform. The read alignment was conducted using TopHat 2.0.13, and relative transcript abundances and differentially expressed genes were determined using the DESeq R package. Results: We identified 14,157 transcripts in esophageal tumors of 4NQO WT and 4NQO S100A14 CKO group mice. Approximately 8% of the transcripts showed differential expression between the esophageal tumors of 4NQO WT and 4NQO S100A 14 CKO group mice, with a fold change ≥1.0 and p value <0.05. Conclusions: Our study represents the first analysis of esophageal tumors derived from S100A14 CKO mice with biologic replicates, generated by RNA-seq.

2022-07-07 | GSE200772 | GEO

Impaired intratumoral natural killer cell function in head and neck carcinoma.

Project description:Natural killer (NK) cells are emerging as unique players in the immune response against cancer; however, only limited data are available on tumor infiltrating NK cells in head and neck squamous cell carcinoma (HNSCC), one of the most common cancer. Occurrence of HNSCC is closely related to the immune microenvironment, and immunotherapy is increasingly being applied to this setting. However, the limited success of this type of treatment in this tumor calls for further investigation in the field. Surgical HNSSC specimens of 32 consecutive patients were mechanically and enzymatically dissociated. Tumor cells were separated from infiltrating cells by short centrifugation and infiltrating NK cells were phenotypically and functionally characterized by multiple antibody staining and flow cytometry. Tumor infiltrating NK cells in HNSCC showed a peculiar phenotype predominantly characterized by increased NKG2A and reduced Siglec-7, NKG2D, NKp30 and CD16 expression. This phenotype was associated with a decreased ability to perform antibody-dependent cellular cytotoxicity (ADCC). However, NK, CD4 and CD8 shared an increment of glucocorticoid-induced tumor necrosis factor-related (GITR) costimulatory receptor which could be exploited for immunotherapy with agonistic anti-GITR antibodies combined with checkpoint inhibitors.

| S-EPMC9630640 | biostudies-literature

Transcriptomic analysis of 4NQO-induced oral squamous cell carcinoma with agonistic anti-CD40 treatment

Project description:To investigate the anti-tumor effect of agonistic anti-CD40, 4NQO-indued OSCC mice with agonistic anti-CD40.

2023-10-23 | GSE217407 | GEO

Genomic analysis of 4NQO-induced mouse oral squamous cell carcinomas Genomic analysis of 4NQO-induced mouse oral squamous cell carcinomas Genomic analysis of 4NQO-induced mouse oral squamous cell carcinomas

Project description:Genomic analysis of 4NQO-induced mouse oral squamous cell carcinomas

| PRJEB32924 | ENA

Intratumoral Microbiome in Head and Neck Paragangliomas.

Project description:Head and neck paragangliomas (HNPGLs) are rare neoplasms arising from paraganglia of the parasympathetic nervous system. HNPGLs are characterized by high vascularity and are located in proximity to major vessels and nerves, which may be potential sources of microbial invasion in these tumors. There have been no studies in the literature on the microbiota in HNPGLs. Investigation of the microbiome associated with paragangliomas is important for understanding tumor pathogenesis. In this study, we investigated the microbiome composition in two sets of HNPGLs. First, 29 fresh frozen (FF) tissues were subjected to 16S rRNA gene sequencing; concurrently, a panel of candidate laboratory-derived contaminants was investigated. Second, we analyzed microbial reads from whole transcriptome sequencing data obtained for 82 formalin-fixed paraffin-embedded (FFPE) HNPGLs. The bacterial diversity in FF tumors was found to be significantly lower than that observed in FFPE HNPGLs. Based on 16S rRNA gene sequencing, only seven bacterial families were identified as potential tumor inhabitants: Bryobacteraceae, Enterococcaceae, Neisseriaceae, Legionellaceae, Vibrionaceae, Obscuribacteraceae, and Mycobacteriaceae. However, RNA-Seq demonstrated higher sensitivity for identifying microbiome composition and revealed abundant bacterial families that partially correlated with those previously described in pheochromocytomas and extra-adrenal paragangliomas. No viruses were found in HNPGLs. In summary, our findings indicated the presence of a microbiome in HNPGLs, comprising a number of bacterial families that overlap with those observed in pheochromocytomas/paragangliomas and glioblastomas.

| S-EPMC11394710 | biostudies-literature

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