A5081375748- Cancer-related molecular mechanisms research
- Head and Neck Cancer Studies
- Cancer Immunotherapy and Biomarkers
- RNA modifications and cancer
- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- Cancer Genomics and Diagnostics
- Viral-associated cancers and disorders
- CAR-T cell therapy research
- Virus-based gene therapy research
- Lymphoma Diagnosis and Treatment
- Cervical Cancer and HPV Research
- Alzheimer's disease research and treatments
- Peptidase Inhibition and Analysis
- MicroRNA in disease regulation
- Colorectal and Anal Carcinomas
- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- Neuroinflammation and Neurodegeneration Mechanisms
- Cultural Heritage Management and Preservation
- Advanced biosensing and bioanalysis techniques
- Computational Drug Discovery Methods
- Ferroptosis and cancer prognosis
- Mathematical Biology Tumor Growth
- Cancer Cells and Metastasis
University of Southampton
2021-2024
ImViA - Imagerie et Vision Artificielle
2024
Janssen (United States)
2023
NIHR CRUK Experimental Cancer Medicine Centre
2021-2023
Cancer Research UK
2022
Southampton General Hospital
2022
Alzheimer’s Disease Neuroimaging Initiative
2020
Abstract Phosphoinositide 3-kinase δ (PI3Kδ) has a key role in lymphocytes, and inhibitors that target this PI3K have been approved for treatment of B cell malignancies 1–3 . Although studies mouse models solid tumours demonstrated PI3Kδ (PI3Kδi) can induce anti-tumour immunity 4,5 , its effect on humans remains unclear. Here we assessed the effects PI3Kδi AMG319 human patients with head neck cancer neoadjuvant, double-blind, placebo-controlled randomized phase II trial (EudraCT no....
Abstract Patients with oropharyngeal squamous cell carcinoma (OPSCC) caused by human papilloma virus (HPV) exhibit a better prognosis than those HPV-negative OPSCC. This study investigated the distinct molecular pathways that delineate from HPV-positive OPSCC to identify biologically relevant therapeutic targets. Bulk mRNA 23 and 39 tumors (n = 62) was sequenced uncover transcriptomic profiles. Differential expression followed gene set enrichment analysis performed outline top enriched...
Background Cancer is characterized by an accumulation of somatic mutations, which a significant subset can generate cancer-specific neoepitopes that are recognized autologous T cells. Such emerging as important targets for cancer immunotherapy, including personalized vaccination strategies. Methods We used whole-exome and RNA sequencing analysis to identify potential neoantigens patient with non-small cell lung cancer. Thereafter, we assessed the T-cell reactivity candidate using long...
Abstract Background The immune peptidome of OPSCC has not previously been studied. Cancer-antigen specific vaccination may improve clinical outcome and efficacy checkpoint inhibitors such as PD1/PD-L1 antibodies. Methods Mapping the HLA ligandome was performed by mass spectrometry (MS) based analysis naturally presented ligands isolated from tumour tissue samples ( n = 40) using immunoaffinity purification. cohort included 22 HPV-positive (primarily HPV-16) 18 HPV-negative samples. A benign...
Abstract The epiCMIT (epigenetically-determined Cumulative MIToses) mitotic clock traces B-cell history via DNA methylation changes in heterochromatin and H3K27me3-containing chromatin. While high scores correlated with poor outcomes CLL MCL, its prognostic significance SMZL remains unknown. Derived from 142 cases using microarrays, values were genomic, transcriptomic, clinical data. EpiCMIT as a continuous variable was significantly higher females ( p =0.02), patients IGHV1-2*04 allele...
A substantial proportion of head and neck squamous cell carcinoma (HNSCC), particularly oropharyngeal (OPSCC), is associated with human papillomavirus (HPV), resulting in distinct molecular phenotypes. In this study, we investigated differential immune checkpoint molecule (ICM) expression by HPV status using RNA sequencing data to identify additional ICM targets that may complement anti-PD1 antibodies.
The tumor microenvironment (TME) comprises all non-tumor elements of cancer and strongly influences disease progression phenotype. To understand biology accurately test new therapeutic strategies, representative models should contain both cells normal the TME. Here, we describe characterize co-culture tumor-derived organoids cancer-associated fibroblasts (CAFs), a major component TME, in matrix-embedded assembloid esophageal adenocarcinoma (EAC). We demonstrate that faithfully recapitulate...
Human papillomavirus 16 (HPV16) is the main cause of oropharyngeal squamous cell carcinoma (OPSCC). To date, links between HPV16 gene expression and adaptive immune responses have not been investigated. We evaluated correlation DNA, RNA transcripts features response by evaluating antibody isotypes against E2, E7 antigens density tumor-infiltrating lymphocytes (TIL). FFPE-tissue from 27/77 p16-positive OPSCC patients was available. DNA were extracted quantified using qPCR for all genes. The...
<p>Clinicopathologic features of patients with OPSCC in Ulm and TCGA cohorts</p>
<p>Cell proliferation upon <i>INHBA</i> knockdown. <b>A,</b> Proliferation of native UDSCC1 cells, Mock KD, KD1/KD2 and UDSCC2 cells as assessed by carboxyfluorescein succinimidyl ester (CFSE) assay flow cytometry. Results are shown mean ± SD the ΔMFI (mean fluorescence intensity) normalized to between t0 t24, or t48 (<i>n</i> = 3). Conditions were compared with using unpaired <i>t</i> test ***, <i>P</i> ≤ 0.001; ****, 0.0001;...
<div>Abstract<p>Patients with oropharyngeal squamous cell carcinoma (OPSCC) caused by human papilloma virus (HPV) exhibit a better prognosis than those HPV-negative OPSCC. This study investigated the distinct molecular pathways that delineate from HPV-positive OPSCC to identify biologically relevant therapeutic targets. Bulk mRNA 23 and 39 tumors (<i>n</i> = 62) was sequenced uncover transcriptomic profiles. Differential expression followed gene set enrichment...
<p>Cell migration upon INHBA knockdown. <b>A,</b> Migration of native UDSCC1 cells, Mock KD, <i>INHBA</i> KD1/KD2 and UDSCC2 cells as assessed by scratch assay. Results are shown mean ± SD the open wound area (<i>n</i> = 3) at baseline (t0), t24, t48. Conditions were compared with using unpaired <i>t</i> test ***, <i>P</i> ≤ 0.001; ****, 0.0001; ns, > 0.05. <b>B,</b> Representative images processed light...
<p>Colony formation ability upon <i>INHBA</i> knockdown. <b>A,</b> Ability for clonal expansion of native UDSCC1 cells, Mock KD, KD1/KD2, and UDSCC2 cells as assessed by colony assay. Colonies between 10 50 were considered small (red) colonies greater big (blue). Results are shown mean ± SEM the number total (<i>n</i> = 3). Conditions compared with using unpaired <i>t</i> test **, <i>P</i> ≤ 0.01; ***, 0.001; ns, > 0.05....
<p>Kaplan–Meier survival analysis and RMST in patients with OPSCC based on <i>INHBA</i> expression levels. <b>A</b> <b>B,</b> Kaplan–Meier plots log-rank test for overall of (<b>A:</b> Ulm cohort, <b>B:</b> TCGA cohort) tumor INHBA expression. Blue indicates low red high expression, as determined using Q3 cutoff. (<b>C–F</b>) defined the area under curve (pink) status...
<p><i>INHBA</i> correlates with stemness attributes. <b>A,</b> Correlation matrix between <i>INHBA</i> and stemness-related markers showing Spearman rho in scaled dots <i>P</i>-value symbols (*, <i>P</i> ≤ 0.05; **, 0.01; ****, 0.0001) the upper triangular values lower matrix. <b>B,</b> Time series of ALDH enzyme activity for Mock KD INHBA KD1/KD2. Results are shown as mean ± SD (mU/mL; <i>n</i> = 3) Δt...
<div>Abstract<p>Patients with oropharyngeal squamous cell carcinoma (OPSCC) caused by human papilloma virus (HPV) exhibit a better prognosis than those HPV-negative OPSCC. This study investigated the distinct molecular pathways that delineate from HPV-positive OPSCC to identify biologically relevant therapeutic targets. Bulk mRNA 23 and 39 tumors (<i>n</i> = 62) was sequenced uncover transcriptomic profiles. Differential expression followed gene set enrichment...
<p>Clinicopathologic features of patients with OPSCC in Ulm and TCGA cohorts</p>
<p>Cell migration upon INHBA knockdown. <b>A,</b> Migration of native UDSCC1 cells, Mock KD, <i>INHBA</i> KD1/KD2 and UDSCC2 cells as assessed by scratch assay. Results are shown mean ± SD the open wound area (<i>n</i> = 3) at baseline (t0), t24, t48. Conditions were compared with using unpaired <i>t</i> test ***, <i>P</i> ≤ 0.001; ****, 0.0001; ns, > 0.05. <b>B,</b> Representative images processed light...
<p>GSEA identifying <i>INHBA</i> as a leading driver of EMT in HPV-negative tumors. <b>A,</b> Dot plot pathways enriched and depleted compared with HPV-positive OPSCC tumor determined by GSEA transcriptomes from <i>n</i> = 62 primary samples (Ulm cohort). Results were ranked according to the NES, dots colored FDR size was number genes. <b>B,</b> top pathway (EMT) showing enrichment score (green curve), position genes (black lines) edge...
<p>Cell death upon <i>INHBA</i> knockdown. <b>A,</b> Cell of native UDSCC1, Mock KD, KD1/KD2 and UDSCC2 cells as assessed by Annexin V/7-AAD staining flow cytometry. Results are shown mean ± SD the percentages dead normalized to UDSCC1 (<i>n</i> = 3). Conditions were compared with using unpaired <i>t</i> test *, <i>P</i> ≤ 0.05; **, 0.01; ****, 0.0001; ns, > 0.05. <b>B,</b> Representative cytometry plots for...
<p><i>INHBA</i> expression in OPSCC tumor and cell lines its correlation with EMT transcription factors. Correlation of <i>INHBA</i> the <i>SNAI1</i> (<b>A</b>), <i>SNAI2</i> (<b>B</b>), <i>TWIST1</i> (<b>C</b>) tumors (Ulm cohort). TPM = transcripts per million. <b>D,</b> Relative mRNA native UDSCC1 (HPV-negative) UDSCC2 (HPV-positive) cells as determined by qRT-PCR normalized...