A5074158782- Peptidase Inhibition and Analysis
- Monoclonal and Polyclonal Antibodies Research
- Protein Degradation and Inhibitors
- vaccines and immunoinformatics approaches
- Immunotherapy and Immune Responses
- Colorectal Cancer Treatments and Studies
- Cancer Genomics and Diagnostics
- Genetic factors in colorectal cancer
- Gastric Cancer Management and Outcomes
- Multiple Myeloma Research and Treatments
- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- CAR-T cell therapy research
Institute of Cancer Research
2019-2023
Queen Mary University of London
2022-2023
Despite biomarker stratification, the anti-EGFR antibody cetuximab is only effective against a subgroup of colorectal cancers (CRCs). This genomic and transcriptomic analysis resistance landscape in 35 RAS wild-type CRCs identified associations NF1 non-canonical RAS/RAF aberrations with primary validated CRC subtypes as non-genetic predictors benefit. Sixty-four percent biopsies acquired harbored no genetic drivers. Most these had switched from cetuximab-sensitive subtype at baseline to...
<h3>Background</h3> Patient derived organoids (PDOs) can be established from colorectal cancers (CRCs) as in vitro models to interrogate cancer biology and its clinical relevance. We applied mass spectrometry (MS) immunopeptidomics investigate neoantigen presentation whether this augmented through interferon gamma (IFNγ) or MEK-inhibitor treatment. <h3>Methods</h3> Four microsatellite stable PDOs chemotherapy refractory one a treatment naïve CRC were expanded replicates with 100 million...
Abstract Background Gastric and gastro-esophageal junction cancers (GCs) frequently recur after resection, but markers to predict recurrence risk are missing. T-cell infiltrates have been validated as prognostic in other cancer types, not GC because of methodological limitations past studies. We aimed define validate the role major subtypes by objective computational quantification. Methods Surgically resected chemotherapy-naïve GCs were split into discovery (n = 327) validation 147)...
Abstract IFNγ alters the immunopeptidome presented on HLA class I (HLA-I), and its activity cancer cells is known to be important for effective immunotherapy responses. We performed proteomic analyses of untreated IFNγ-treated colorectal patient-derived organoids combined this with transcriptomic HLA-I immunopeptidomics data dissect mechanisms that lead remodeling through IFNγ. IFNγ-induced changes in abundance source proteins, switching from constitutive immunoproteasome, differential...
Epidermal growth factor receptor antibodies (EGFR-Abs) confer a survival benefit in patients with RAS wild-type metastatic colorectal cancer (mCRC), but resistance invariably occurs. Previous data showed that only minority of cells harboured known genetic drivers when clinical to single-agent EGFR-Abs had evolved, supporting the activity non-genetic mechanisms. Here, we used error-corrected ctDNA-sequencing (ctDNA-Seq) 40 genes identify and whether resistance-gap (a lack detectable...
Abstract IFNγ alters the immunopeptidome presented on HLA class I (HLA-I), and its activity cancer cells is known to be important for effective immunotherapy responses. We performed proteomic analyses of untreated IFNγ-treated colorectal patient-derived organoids (PDOs) combined this with transcriptomic HLA-I immunopeptidomics data dissect mechanisms that lead remodeling through IFNγ. IFNγ-induced changes in abundance source proteins, switching from constitutive- immunoproteasome,...
<p>Supplementary Figure and Table Legends 1-2</p>
<p>RNA, protein and peptide data for CRC05</p>
<p>Supplemental Figure 2. Additional internal validation of difference in amino acid features peptides between untreated and IFNγ-treated conditions.</p>
<p>Supplementary Figure 1. Effect of relative peptide position within protein on abundance changes under IFNγ treatment.</p>
<p>RNA, protein and peptide data for CRC01</p>
IFNγ alters the immunopeptidome presented on HLA class I (HLA-I), and its activity cancer cells is known to be important for effective immunotherapy responses. We performed proteomic analyses of untreated IFNγ-treated colorectal patient-derived organoids combined this with transcriptomic HLA-I immunopeptidomics data dissect mechanisms that lead remodeling through IFNγ. IFNγ-induced changes in abundance source proteins, switching from constitutive immunoproteasome, differential upregulation...
<p>RNA, protein and peptide data for CRC05</p>
<p>RNA, protein and peptide data for CRC04</p>
<p>RNA, protein and peptide data for CRC01</p>
<p>RNA, protein and peptide data for CRC04</p>
<div>Abstract<p>IFNγ alters the immunopeptidome presented on HLA class I (HLA-I), and its activity cancer cells is known to be important for effective immunotherapy responses. We performed proteomic analyses of untreated IFNγ-treated colorectal patient-derived organoids combined this with transcriptomic HLA-I immunopeptidomics data dissect mechanisms that lead remodeling through IFNγ. IFNγ-induced changes in abundance source proteins, switching from constitutive immunoproteasome,...
<p>Supplementary Figure and Table Legends 1-2</p>
<p>Supplementary Figure 1. Effect of relative peptide position within protein on abundance changes under IFNγ treatment.</p>
<p>Supplemental Figure 2. Additional internal validation of difference in amino acid features peptides between untreated and IFNγ-treated conditions.</p>