Ayse U. Akarca
A5067431043- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Immune cells in cancer
- Neuroendocrine Tumor Research Advances
- Lung Cancer Research Studies
- Lymphoma Diagnosis and Treatment
- Gastrointestinal Tumor Research and Treatment
- Synthesis and pharmacology of benzodiazepine derivatives
- Cancer Genomics and Diagnostics
- Lung Cancer Treatments and Mutations
- Immune Cell Function and Interaction
- Protein Degradation and Inhibitors
- Monoclonal and Polyclonal Antibodies Research
- Immune responses and vaccinations
- Cancer therapeutics and mechanisms
- Radiomics and Machine Learning in Medical Imaging
- Ferroptosis and cancer prognosis
- CAR-T cell therapy research
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Single-cell and spatial transcriptomics
- Chronic Lymphocytic Leukemia Research
- DNA Repair Mechanisms
- Neutropenia and Cancer Infections
- Hepatocellular Carcinoma Treatment and Prognosis
University College London
2016-2025
University College Hospital
2017-2025
Royal London Hospital
2016-2024
CRUK Lung Cancer Centre of Excellence
2016-2024
University of Pennsylvania
2023
University College London Hospitals NHS Foundation Trust
2017-2022
London Cancer
2017-2021
University of London
2020
Cancer Research UK
2017
UCL Australia
2014
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...
ADAPTeR is a prospective, phase II study of nivolumab (anti-PD-1) in 15 treatment-naive patients (115 multiregion tumor samples) with metastatic clear cell renal carcinoma (ccRCC) aiming to understand the mechanism underpinning therapeutic response. Genomic analyses show no correlation between molecular features and response, whereas ccRCC-specific human endogenous retrovirus expression indirectly correlates clinical T receptor (TCR) analysis reveals significantly higher number expanded TCR...
In addition to helper and regulatory potential, CD4
Patients with neuroblastoma infused GD2-directed CAR-T cells experienced immune activation and transient tumor regressions without neurotoxicity.
Background Modulation of adaptive immunity may underscore the efficacy trans-arterial chemoembolization (TACE). We evaluated influence TACE on T-cell function by phenotypic lymphocyte characterization in samples patients undergoing surgery with (T+) or without (T-) prior-TACE treatment. Methods profiled intratumoral (IT), peritumoral (PT) and non-tumoral (NT) background tissue to evaluate regulatory CD4+/FOXP3+ (T-reg) immune-exhausted CD8+/PD-1+ T-cells across T+ (n=58) T− (n=61). performed...
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 Despite the many advances in treatment of hematologic malignancies over past decade, outcomes refractory lymphomas remain poor. One potential strategy this patient population is specific targeting IL2R-α (CD25), which overexpressed on lymphoma and leukemic cells, using antibody–drug conjugates (ADC). ADCT-301 an ADC composed human IgG1 HuMax-TAC against CD25, stochastically conjugated through a dipeptide cleavable linker to pyrrolobenzodiazepine (PBD) dimer warhead with...
Abstract APOBEC3 enzymes are cytosine deaminases implicated in cancer. Precisely when expression is induced during cancer development remains to be defined. Here we show that specific genes upregulated breast ductal carcinoma situ, and preinvasive lung lesions coincident with cellular proliferation. We observe evidence of APOBEC3-mediated subclonal mutagenesis propagated from TRACERx invasive non–small cell (NSCLC) lesions. find APOBEC3B exacerbates DNA replication stress chromosomal...
The linear ubiquitin chain assembly complex (LUBAC), composed of HOIP, HOIL-1 and SHARPIN, is required for optimal TNF-mediated gene activation to prevent cell death induced by TNF. Here, we demonstrate that keratinocyte-specific deletion HOIP or (E-KO) results in severe dermatitis causing postnatal lethality. We provide genetic pharmacological evidence the lethal HoipE-KO Hoil-1E-KO mice caused TNFR1-induced, caspase-8-mediated apoptosis occurs independently kinase activity RIPK1. In...
Programmed cell death ligand-1 immunohistochemical detection (PD-L1 IHC) is a putative predictor of response to PD-1/PD-L1-targeted checkpoint inhibitors. However, there no gold standard assay in hepatocellular carcinoma (HCC). We evaluated 5 PD-L1 IHC platforms (E1LN3, 28-8, 22c3, SP263 and SP142) 100 HCCs reporting expression malignant (M) tumour-infiltrating immune cells (TICs) non-tumorous cirrhotic tissues (NTICs). found substantial inter-assay heterogeneity detecting M (R2 =...
Abstract Before squamous cell lung cancer develops, precancerous lesions can be found in the airways. From longitudinal monitoring, we know that only half of such become cancer, whereas a third spontaneously regress. Although recent studies have described presence an active immune response high-grade lesions, mechanisms underpinning clinical regression remain unknown. Here, show host surveillance is strongly implicated lesion regression. Using bronchoscopic biopsies from human subjects, find...
Abstract Beyond tertiary lymphoid structures, a significant number of immune-rich areas without germinal center-like structures are observed in non–small cell lung cancer. Here, we integrated transcriptomic data and digital pathology images to study the prognostic implications, spatial locations, constitution immune rich (immune hotspots) cohort 935 patients with cancer from The Cancer Genome Atlas. A high intratumoral hotspot score, which measures proportion hotspots interfacing tumor...
Patient-derived xenograft (PDX) models are widely used in cancer research. To investigate the genomic fidelity of non-small cell lung PDX models, we established 48 from 22 patients enrolled TRACERx study. Multi-region tumor sampling increased successful engraftment and most were histologically similar to their parent tumor. Whole-exome sequencing enabled comparison tumors provide an adapted mouse reference genome for improved removal NOD scid gamma (NSG) mouse-derived reads data. model...
Few studies were conducted investigating the immunological profiles in gastrointestinal stromal tumors (GIST). Adaptive and innate immune cells are present tumor microenvironment, indicating GIST as inflamed tumors. In addition, murine models suggested a potential interaction between components imatinib. this retrospective study, profile was investigated through silico analysis immunohistochemistry (IHC), exploring basis for immunotherapy approaches. Gene expression (GEP) from 31...
Abstract Myasthenia gravis (MG) is an autoimmune disease characterized by impaired neuromuscular signaling due to autoantibodies targeting the acetylcholine receptor. Although its auto-antigens and effector mechanisms are well defined, cellular molecular drivers underpinning MG remain elusive. Here, we employed high-dimensional single-cell mass spectral cytometry of blood thymus samples from patients in combination with supervised unsupervised machine-learning tools gain insight into immune...
In vivo IL-17A activity is elevated in active tuberculosis and may be a therapeutic target to attenuate disease-associated immunopathology.
BackgroundIntratumoural heterogeneity (ITH) is well recognised in prostate cancer (PC), but its role high-risk disease uncertain. A prospective, single-arm, translational study using targeted multiregion biopsies was carried out to genomic and T-cell ITH clinically PC aiming identify drivers potential therapeutic strategies.Patients methodsForty-nine men with elevated prostate-specific antigen multiparametric-magnetic resonance imaging detected underwent image-guided transperineal biopsy....
Dendritic cells (DC) are specialized mononuclear phagocytes that link innate and adaptive immunity. They comprise two principal subsets: plasmacytoid DC (pDC) conventional (cDC). Understanding the generation, differentiation, migration of cDC is critical for immune homeostasis. Through human in vivo deuterium-glucose labeling, we observed rapid appearance AXL+ Siglec6+ (ASDC) bloodstream. ASDC circulate ∼2.16 days, while cDC1 DC2 ∼1.32 ∼2.20 respectively, upon release from bone marrow....