Kristiana Grigoriadis
A5058521816- Immune cells in cancer
- Immunotherapy and Immune Responses
- Cancer Genomics and Diagnostics
- Immune responses and vaccinations
- Cancer Immunotherapy and Biomarkers
- Lung Cancer Treatments and Mutations
- Immune Cell Function and Interaction
- RNA modifications and cancer
- Ferroptosis and cancer prognosis
- Single-cell and spatial transcriptomics
- Radiomics and Machine Learning in Medical Imaging
- Cancer-related molecular mechanisms research
- Genomics and Phylogenetic Studies
- Molecular Biology Techniques and Applications
- Prostate Cancer Treatment and Research
- Epigenetics and DNA Methylation
- AI in cancer detection
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- Genetic factors in colorectal cancer
- Lung Cancer Diagnosis and Treatment
- Mathematical Biology Tumor Growth
- Nutrition and Health in Aging
- Body Composition Measurement Techniques
- Lymphoma Diagnosis and Treatment
University College London
2022-2025
The Francis Crick Institute
2022-2025
Cancer Research UK
2022-2025
London Cancer
2022-2025
CRUK Lung Cancer Centre of Excellence
2022-2025
Aarhus University
2023
Aarhus University Hospital
2023
University College Hospital
2023
Cancer Institute (WIA)
2023
Breast Cancer Now
2022
Lung cancer is the leading cause of cancer-associated mortality worldwide
Abstract B cells are frequently found in the margins of solid tumours as organized follicles ectopic lymphoid organs called tertiary structures (TLS) 1,2 . Although TLS have been to correlate with improved patient survival and response immune checkpoint blockade (ICB), underlying mechanisms this association remain elusive Here we investigate lung-resident cell responses patients from TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) other lung cancer cohorts, a...
Metastatic disease is responsible for the majority of cancer-related deaths
Abstract Understanding the role of tumor microenvironment (TME) in lung cancer is critical to improving patient outcomes. We identified four histology-independent archetype TMEs treatment-naïve early-stage using imaging mass cytometry TRACERx study (n = 81 patients/198 samples/2.3 million cells). In immune-hot adenocarcinomas, spatial niches T cells and macrophages increased with clonal neoantigen burden, whereas such an increase was observed for plasma B immune-excluded squamous cell...
Abstract Circulating tumor DNA (ctDNA) detection can predict clinical risk in early-stage tumors. However, applications are constrained by the sensitivity of clinically validated ctDNA approaches. NeXT Personal is a whole-genome-based, tumor-informed platform that has been analytically for ultrasensitive at 1–3 ppm with 99.9% specificity. Through an analysis 171 patients lung cancer from TRACERx study, we detected pre-operatively within 81% adenocarcinoma (LUAD), including 53% those...
Abstract Human tumors are diverse in their natural history and response to treatment, which part results from genetic transcriptomic heterogeneity. In clinical practice, single-site needle biopsies used sample this diversity, but cancer biomarkers may be confounded by spatiogenomic heterogeneity within individual tumors. Here we investigate clonally expressed genes as a solution the sampling bias problem analyzing multiregion whole-exome RNA sequencing data for 450 tumor regions 184 patients...
Abstract Recognition and elimination of pathogens cancer cells depend on the adaptive immune system. Thus, accurate quantification subsets is vital for precision medicine. We present lymphocyte estimation from nucleotide sequencing (ImmuneLENS), which estimates T cell B fractions, class switching clonotype diversity whole-genome data at depths as low 5× coverage. By applying ImmuneLENS to 100,000 Genomes Project, we identify genes enriched with somatic mutations in cell-rich tumors,...
Chimeric antigen receptor (CAR)-T cells can induce powerful immune responses in patients with hematological malignancies but have had limited success against solid tumors. This is part due to the immunosuppressive tumor microenvironment (TME) which limits activity of tumor-infiltrating lymphocytes (TILs) including CAR-T cells. We developed a next-generation armored CAR (F i-CAR) targeting tyrosine kinase-like orphan 1 (ROR1), expressed at high levels range aggressive tumors poorly prognostic...
Abstract Sequencing of cell-free DNA (cfDNA) in cancer patients’ plasma offers a minimally-invasive solution to detect tumor cell genomic alterations aid real-time clinical decision-making. The reliability copy number detection decreases at lower cfDNA fractions, limiting utility earlier stages the disease. To test novel strategy for allelic imbalance, we developed prostate bespoke assay, PCF_SELECT, that includes an innovative sequencing panel covering ∼25 000 high minor allele frequency...
Abstract Intra-tumour heterogeneity provides the fuel for evolution and selection of subclonal tumour cell populations. However, accurate inference architecture reconstruction evolutionary history from bulk DNA sequencing data remains challenging. Sequencing alignment artefacts cannot be distinguished real cancer somatic mutations errors in identification copy number alterations or complex events (e.g. mutation losses) affect estimated cellular prevalence mutations, leading to clustering...
Abstract Despite initial responses to hormone treatment, metastatic prostate cancer invariably evolves a lethal state. To characterize the intra-patient evolutionary relationships of metastases that evade we perform genome-wide copy number profiling and bespoke approaches targeting androgen receptor (AR) on 167 regions from 11 organs harvested post-mortem 10 men who died cancer. We identify diverse patient-unique alterations clustering around AR in every patient with evidence independent...
<p>Supplementary Figures 1-22 with the corresponding figure legends inline. Supplementary Figure S1. TRACERx 100 imaging mass cytometry cohort. S2. Analysis of data. S3. Characterisation cell subtypes and spatial cellular communities in non-small lung cancer. S4. Clinicogenomic correlations communities. S5. TME class associations types clinical variables. S6. Cancer cell-intrinsic -extrinsic features associated immune infiltration. S7. Spatial, histological metabolic...
The canonical model of tumor suppressor gene (TSG)-mediated oncogenesis posits that loss both alleles is necessary for inactivation. Here, through allele-specific analysis sequencing data from 48,179 cancer patients, we define the prevalence, selective pressure for, and functional consequences biallelic inactivation across TSGs. TSGs largely assort into distinct classes associated with either pan-cancer (Class 1) or lineage-specific 2) patterns selection loss, although some are predominantly...
Abstract Recent breakthroughs in phylogenetic analysis of bulk tissue have allowed researchers to reconstruct the evolutionary histories tumours. The hope is that knowledge order and timing genetic mutations will allow us characterise properties early-stage cancer cells, better identify target them. This complicated by phenomenon tumour plasticity, ability cells acquire hallmarks via mechanisms other than heritable mutation. In a with only heritability, changes cell phenotype would occur as...
Abstract Background: Outgrowth of resistance cancer cell populations is a common mechanism therapy failure in oncology. Effective personalised medicine relies on targeting ubiquitous aberrations; however, tumours are highly heterogenous. Liquid biopsies have the potential to provide representative tumour sampling at regular intervals through disease course, but extensive interrogation longitudinal clonal evolution has been lacking, particularly for patients curative pathway. Methods: We...
Abstract Both single nucleotide variants (SNVs) and somatic copy number alterations (SCNAs) accumulate in cancer cells during tumor development, fuelling clonal evolution. However, accurate inference of their coevolution from bulk DNA sequencing is challenging. We present ALPACA (ALlele-specific Phylogenetic Analysis clone Copy Alterations), a novel algorithm to allow the practical SNV SCNA coevolution. framed as an optimisation problem, that takes input sample mixtures phylogenetic tree...
Abstract Lung carcinoma in situ (CIS) lesions, as precursors to squamous cell carcinoma, exhibit microscopic uniformity while displaying diverse clinical trajectories. Half of these lesions progress invasive cancer, the remaining half either regress or remain indolent. Previous genomic profiling efforts have elucidated progression-specific changes against a backdrop inherent heterogeneity and notable chromosomal instability signatures. Here, we present novel approach by analyzing...
<p>IMC workflow defines the single-cell spatial landscape of NSCLC tumor microenvironment. <b>A,</b> TRACERx 100 IMC cohort. We developed and applied two antibody panels, Pan-immune T cells stroma, to tissue microarrays (TMA) from clinical samples collected at surgical resection (created with BioRender.com). <b>B,</b> Targets antibodies described in this study. Bold text indicates targets detected both panels. <b>C,</b> data were acquired stained...
<p>Spatial features associated with neoantigen burden and immune low TMEs. <b>A,</b> Correlation of densities spatial cellular communities the expressed clonal, subclonal total neoantigens predicted to bind intact HLA alleles, after accounting for LOH, in LUAD (<i>n</i> = 31, 51 tumor cores) LUSC 17, 37 cores). Bar plot shows median whiskers extending 75th percentile. <b>B,</b> Comparison a given TME class compared all other classes combined. LUAD:...
<p>Four TME classes in NSCLC defined by immune composition tumor nests and surrounding stroma. <b>A,</b> Tumor cores were classified into four classes, derived clustering cell densities the nest Only LUAD (<i>n</i> = 65 cores, 35 tumors) LUSC 48, 23 are featured, corresponding clinical annotations displayed. Regional growth patterns shown for LUAD: lepidic (low grade), acinar papillary (mid-grade), solid cribriform (high grade). <b>B,</b>...