James L. Reading
A5089988286- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Cancer Genomics and Diagnostics
- Immune cells in cancer
- CAR-T cell therapy research
- Immune responses and vaccinations
- Immune Cell Function and Interaction
- Radiomics and Machine Learning in Medical Imaging
- T-cell and B-cell Immunology
- Lung Cancer Treatments and Mutations
- Single-cell and spatial transcriptomics
- Medical Imaging Techniques and Applications
- Bladder and Urothelial Cancer Treatments
- Monoclonal and Polyclonal Antibodies Research
- RNA modifications and cancer
- Ferroptosis and cancer prognosis
- Renal cell carcinoma treatment
- Mesenchymal stem cell research
- Neonatal Respiratory Health Research
- Multiple Myeloma Research and Treatments
- Cancer Cells and Metastasis
- Pancreatic function and diabetes
- Immunodeficiency and Autoimmune Disorders
- HIV Research and Treatment
- Pancreatic and Hepatic Oncology Research
CRUK Lung Cancer Centre of Excellence
2017-2025
University College London
2016-2025
London Cancer
2017-2025
Cancer Research UK
2017-2025
Immune Regulation (United Kingdom)
2024
The London College
2024
Allen Institute
2024
Cancer Institute (WIA)
2020-2024
Allen Institute for Immunology
2023
King's College London
2007-2021
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.
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...
Abstract Murine tissues harbor signature γδ T cell compartments with profound yet differential impacts on carcinogenesis. Conversely, human tissue-resident cells are less well defined. In the present study, we show that lung a resident Vδ1 population. Moreover, demonstrate memory and effector phenotypes were enriched in tumors compared nontumor tissues. Intratumoral possessed stem-like features skewed toward cytolysis helper type 1 function, akin to intratumoral natural killer CD8 +...
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 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,...
Cancer mutations generate novel (neo-)peptides recognised by T cells, but the determinants of recognition are not well characterised. The difference in predicted class I major histocompatibility complex (MHC-I) binding affinity between wild-type and corresponding mutant peptides (differential agretopicity index; DAI) may reflect clinically relevant cancer peptide immunogenicity. Our aim was to explore relationship DAI, measures immune infiltration patient outcomes advanced cancer.
Abstract Frameshift insertion/deletions (fs-indels) are an infrequent but highly immunogenic mutation subtype. Although fs-indels degraded through the nonsense-mediated decay (NMD) pathway, we hypothesise that some escape degradation and elicit anti-tumor immune responses. Using allele-specific expression analysis, expressed enriched in genomic positions predicted to NMD, associated with higher protein expression, consistent (NMD-escape). Across four independent melanoma cohorts, NMD-escape...
Abstract CD8 + T cell reactivity towards tumor mutation-derived neoantigens is widely believed to facilitate the antitumor immunity induced by immune checkpoint blockade (ICB). Here we show that broadening in number of neoantigen-reactive (NART) populations between pre-treatment 3-weeks post-treatment distinguishes patients with controlled disease compared progressive metastatic urothelial carcinoma (mUC) treated PD-L1-blockade. The longitudinal analysis peripheral recognition...
Studies of human lung development have focused on epithelial and mesenchymal cell types function, but much less is known about the developing immune cells, even though airways are a major site mucosal immunity after birth. An unanswered question whether tissue-resident cells play role in shaping tissue as it develops utero. Here, we profiled embryonic fetal using scRNA-seq, smFISH, immunohistochemistry. At stage, observed an early wave innate including lymphoid natural killer myeloid lineage...
Abstract Neoantigen vaccines are under investigation for various cancers, including epidermal growth factor receptor ( EGFR )-driven lung cancers 1,2 . We tracked the phylogenetic history of an mutant cancer treated with erlotinib, osimertinib, radiotherapy and a personalized neopeptide vaccine (NPV) targeting ten somatic mutations, exon 19 deletion (ex19del). The ex19del mutation was clonal, but is likely to have appeared after whole-genome doubling (WGD) event. Following osimertinib NPV...
The Fourth Expert Meeting of the Mesenchymal Stem Cells in Solid Organ Transplantation (MiSOT) Consortium took place Barcelona on October 19 and 20, 2012. This meeting focused translation preclinical data into early clinical settings. position paper highlights main topics explored safety efficacy mesenchymal stem cells as a therapeutic agent solid organ transplantation emphasizes issues (proper timing, concomitant immunossupression, source immunogenicity cells, oncogenicity) that have been...
A major goal of immunotherapy remains the control pathogenic T cell responses that drive autoimmunity and allograft rejection. Adherent progenitor cells, including mesenchymal stromal cells (MSCs) multipotent adult (MAPCs), represent attractive immunomodulatory therapy candidates currently active in clinical trials. MAPCs can be distinguished from MSCs on basis cellular phenotype, size, transcriptional profile, expansion capacity. However, despite their ongoing evaluation autoimmune...
Defective immune homeostasis in the balance between FOXP3+ regulatory T cells (Tregs) and effector is a likely contributing factor loss of self-tolerance observed type 1 diabetes (T1D). Given importance interleukin-2 (IL-2) signaling generation function Tregs, observations that polymorphisms genes IL-2 pathway associate with T1D some individuals exhibit reduced indicate impairment this may play role Treg dysfunction pathogenesis T1D. Here, we have examined sensitivity CD4+ T-cell subsets 70...
Despite the advances in cancer immunotherapy, only a fraction of patients with bladder exhibit responses to checkpoint blockade, highlighting need better understand drug resistance and identify rational immunotherapy combinations. However, accessibility tumor prior during therapy is major limitation understanding immune microenvironment (TME). Herein, we identified urine-derived lymphocytes (UDLs) as readily accessible source T cells 32 muscle invasive (MIBC). We observed that effector CD8+...
T-cell depletion therapy is used to prevent acute allograft rejection, treat autoimmunity and create space for bone marrow or hematopoietic cell transplantation. The evolved response loss a transient increase in IL-7 that drives compensatory homeostatic proliferation (HP) of mature T cells. Paradoxically, the exaggerated form this process occurs following lymphodepletion expands effector T-cells, often causing immunological tolerance results rapid graft autoimmunity, exacerbated...
Abstract Checkpoint inhibitors (CPIs) augment adaptive immunity. Systematic pan-tumor analyses may reveal the relative importance of tumour cell intrinsic and microenvironmental features underpinning CPI sensitization. Here we collated whole-exome transcriptomic data for >1000 CPI-treated patients across eight tumor-types, utilizing standardized bioinformatics-workflows clinical outcome-criteria to validate multivariate predictors CPI-sensitization. Clonal-TMB was strongest predictor...