Charles Swanton
A5016475369- Cancer Genomics and Diagnostics
- Cancer Immunotherapy and Biomarkers
- Lung Cancer Treatments and Mutations
- Immunotherapy and Immune Responses
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Genetic factors in colorectal cancer
- DNA Repair Mechanisms
- Microtubule and mitosis dynamics
- Renal cell carcinoma treatment
- Genomic variations and chromosomal abnormalities
- Radiomics and Machine Learning in Medical Imaging
- SARS-CoV-2 and COVID-19 Research
- Monoclonal and Polyclonal Antibodies Research
- Gene expression and cancer classification
- Immune Cell Function and Interaction
- Cancer Cells and Metastasis
- Single-cell and spatial transcriptomics
- COVID-19 Clinical Research Studies
- Immune cells in cancer
- Ferroptosis and cancer prognosis
- Genomics and Chromatin Dynamics
- CAR-T cell therapy research
- BRCA gene mutations in cancer
- Bioinformatics and Genomic Networks
The Francis Crick Institute
2016-2025
Cancer Research UK
2016-2025
University College London
2016-2025
London Cancer
2016-2025
CRUK Lung Cancer Centre of Excellence
2016-2025
Royal London Hospital
2016-2025
University College London Hospitals NHS Foundation Trust
2017-2024
University College Hospital
2017-2024
Royal Marsden Hospital
2004-2023
Royal Ottawa Mental Health Centre
2023
Intratumor heterogeneity may foster tumor evolution and adaptation hinder personalized-medicine strategies that depend on results from single tumor-biopsy samples.
The cellular ancestry of tumor antigens One contributing factor in antitumor immunity is the repertoire neoantigens created by genetic mutations within cells. Like corresponding mutations, these show intratumoral heterogeneity. Some are present all cells (clonal), and others only a fraction (subclonal). In study lung cancer melanoma, McGranahan et al. found that high burden clonal correlated with improved patient survival, an increased presence tumor-infiltrating lymphocytes, durable...
Among patients with non-small-cell lung cancer (NSCLC), data on intratumor heterogeneity and genome evolution have been limited to small retrospective cohorts. We wanted prospectively investigate in relation clinical outcome determine the clonal nature of driver events evolutionary processes early-stage NSCLC.
Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, polymorphic nature locus has precluded accurate HLA copy-number analysis. Here, we heterozygosity in (LOHHLA), computational tool determine allele-specific copy number from sequencing data. Using LOHHLA, find that LOH occurs 40% non-small-cell lung cancers (NSCLCs) and associated with high subclonal neoantigen burden,...
Analysis of somatic mutations provides insight into the mutational processes that have shaped cancer genome, but such analysis currently requires large cohorts. We develop deconstructSigs, which allows identification signatures within a single tumor sample. Application deconstructSigs identifies samples with DNA repair deficiencies and reveals distinct dynamic molding genome in esophageal adenocarcinoma compared to squamous cell carcinomas. confers ability define driven by environmental...
Spatial and temporal dissection of the genomic changes occurring during evolution human non-small cell lung cancer (NSCLC) may help elucidate basis for its dismal prognosis. We sequenced 25 spatially distinct regions from seven operable NSCLCs found evidence branched evolution, with driver mutations arising before after subclonal diversification. There was pronounced intratumor heterogeneity in copy number alterations, translocations, associated APOBEC cytidine deaminase activity. Despite...
Early cancer detection could identify tumors at a time when outcomes are superior and treatment is less morbid. This prospective case-control sub-study (from NCT02889978 NCT03085888) assessed the performance of targeted methylation analysis circulating cell-free DNA (cfDNA) to detect localize multiple types across all stages high specificity.
Combination immune checkpoint blockade has demonstrated promising benefit in lung cancer, but predictors of response to combination therapy are unknown. Using whole-exome sequencing examine non-small-cell cancer (NSCLC) treated with PD-1 plus CTLA-4 blockade, we found that high tumor mutation burden (TMB) predicted improved objective response, durable benefit, and progression-free survival. TMB was independent PD-L1 expression the strongest feature associated efficacy multivariable analysis....
Zoonotic introduction of novel coronaviruses may encounter preexisting immunity in humans. Using diverse assays for antibodies recognizing SARS-CoV-2 proteins, we detected humoral immunity. spike glycoprotein (S)-reactive were detectable using a flow cytometry-based method SARS-CoV-2-uninfected individuals and particularly prevalent children adolescents. They predominantly the immunoglobulin G (IgG) class targeted S2 subunit. By contrast, infection induced higher titers S-reactive IgG...
The focus of tumour-specific antigen analyses has been on single nucleotide variants (SNVs), with the contribution small insertions and deletions (indels) less well characterised. We investigated whether frameshift nature indel mutations, which create novel open reading frames a large quantity mutagenic peptides highly distinct from self, might contribute to immunogenic phenotype.
Clear-cell renal cell carcinoma (ccRCC) exhibits a broad range of metastatic phenotypes that have not been systematically studied to date. Here, we analyzed 575 primary and 335 biopsies across 100 patients with ccRCC, including two cases sampledat post-mortem. Metastatic competence was afforded by chromosome complexity, identify 9p loss as highly selected event driving metastasis ccRCC-related mortality (p = 0.0014). Distinct patterns dissemination were observed, rapid progression multiple...