A5014363589- Cancer Immunotherapy and Biomarkers
- Colorectal Cancer Treatments and Studies
- Cancer Treatment and Pharmacology
- Immunotherapy and Immune Responses
- Neuroblastoma Research and Treatments
- Lung Cancer Treatments and Mutations
- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- Multiple Myeloma Research and Treatments
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Genetics, Bioinformatics, and Biomedical Research
- Cancer Genomics and Diagnostics
- vaccines and immunoinformatics approaches
- Pancreatic and Hepatic Oncology Research
- Vaccine Coverage and Hesitancy
- Multiple and Secondary Primary Cancers
- Metabolism, Diabetes, and Cancer
- Berberine and alkaloids research
- Lung Cancer Research Studies
- HER2/EGFR in Cancer Research
- Chronic Lymphocytic Leukemia Research
- Bladder and Urothelial Cancer Treatments
- Cancer, Stress, Anesthesia, and Immune Response
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- T-cell and B-cell Immunology
Roche (Switzerland)
2021-2024
Queen Mary University of London
2023
Lung-resident immune cells, spanning both innate and adaptive compartments, preserve the integrity of respiratory barrier, but become pathogenic if dysregulated1. Current in vitro organoid models aim to replicate interactions between alveolar epithelium cells have not yet incorporated lung-specific critical for tissue residency2. Here we address this shortcoming by describing human lung immuno-organoids (LIO) that contain an autologous tissue-resident lymphoid compartment, primarily composed...
Abstract Background Large language models (LLMs) have emerged as transformative technologies, revolutionizing natural understanding and generation across various domains, including medicine. In this study, we investigated the capabilities, limitations, generalizability of Generative Pre-trained Transformer (GPT) in analyzing unstructured patient notes from large healthcare datasets to identify immune-related adverse events (irAEs) associated with use immune checkpoint inhibitor (ICI)...
Abstract The systemic immunological effects of combining anti-CTLA4 therapy with PD-(L)1 blockade remain incompletely characterized, despite the widespread use this combination in treating various solid tumors across multiple stages disease. Herein, we investigated additive impact on peripheral immune signatures patients undergoing blockade, using blood samples from a cohort receiving checkpoint inhibitor for advanced tumors. We performed in-parallel analysis mononuclear cells (PBMC)...
PURPOSE Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, yet their use is associated with immune-related adverse events (irAEs). Estimating the prevalence and patient impact of these irAEs in real-world data setting critical for characterizing benefit/risk profile ICI therapies beyond clinical trial population. Diagnosis codes, such as International Classification Diseases do not comprehensively illustrate a patient's care journey offer no insight into drug-irAE...
Abstract Background Dose-limiting toxicities significantly impact the benefit/risk profile of many drugs. Whole genome sequencing (WGS) in patients receiving drugs with dose-limiting can identify therapeutic hypotheses to prevent these toxicities. Chemotherapy-induced peripheral neuropathy (CIPN) is a common neurological toxicity chemotherapies no effective approach for prevention. Methods We conducted genetic study time-to-first event using 30× germline WGS data from whole blood samples...
2667 Background: ICIs may cause severe skin toxicity associated with significant patient (pt) impact. Published data suggests Asian pts might be at higher risk of immune-related adverse events (SirAEs). Variation in human leukocyte antigen (HLA) is known to predispose autoimmune (AI) conditions, but there limited understand genetic drivers SirAEs. Methods: The incidence SirAEs was correlated 30 HLA alleles interest 2 cohorts totaling 18 (Dermatitis bullous n=4, Erythema multiforme n=10,...
2662 Background: IrAEs associated with immune checkpoint inhibitors (ICIs) can result in morbidity and mortality. The incidence, spectrum, risk factors for irAEs are usually reported from retrospective studies clinical trials, which typically exclude patients (pts) pre-existing autoimmune disease (AD). prevalence a diverse, pan-tumor, real-world setting is not well understood. Methods: From 06/2021 to 2/2023, we prospectively enrolled pts receiving ICIs (alone or combination as...
2571 Background: Fatigue is the most common side effect of immune checkpoint inhibitor (ICI) therapy. Despite its prevalence, mechanisms underlying ICI-associated fatigue are poorly understood. In this study, we characterized dynamic changes in peripheral cell populations and cytokines to identify biomarkers fatigue. Methods: We prospectively collected clinical data blood samples from patients with solid tumors at a single institution who received ICIs between July 2021 November 2023. Blood...
<h3>Background</h3> The cancer-immunity cycle (CIC) provides a staged framework for understanding the interplay between immune response and disease (figure 1).<sup>1</sup> Precise quantification of gene expression in each stage contribution to physiological effects remains elusive. This study aims personalize CIC profiles pinpoint stages informing precision therapy diagnostics. <h3>Methods</h3> Data was anonymized from prospective, randomized trials exploring atezolizumab advanced urothelial...
<h3>Background</h3> Checkpoint inhibitors (CPIs) have significantly enhanced cancer treatment, yet formation of antidrug antibodies (ADA) can reduce drug efficacy and lead to increased immune toxicity.<sup>1</sup> Identifying biomarkers predictive ADA is crucial optimize administration CPIs. Human leukocyte antigen (HLA) genes are responsible for presentation antigens T cells harbor substantial inter-patient variation. A recent study<sup>2</sup> identified allelic variation in the...
Background The association between safety and efficacy of immune checkpoint inhibitors is known, but the correlation severity impact specific organ involvement by immune-related adverse events (irAE) cancer outcomes poorly understood. Most irAEs are mild-to-moderate severe may pose clinical management challenges affect patient outcomes. Methods We assessed irAE grade (G) with overall survival (OS) in 9,521 patients across 14 studies involving atezolizumab as mono (IO) or chemo/targeted...
Abstract Natural killer (NK) cells are educated through the binding of immunoglobulin like receptors (KIR) to human leukocyte antigen (HLA) proteins, but it is unknown whether presence these highly diverse KIR/HLA interactions influence responses immunotherapy in solid tumors. We report herein two observations that shed light on NK cell function and abundance anti-tumor immune responses. In patients with non-small lung cancer treated anti-PD-L1 therapy, we found individuals carrying HLA-C1...
2588 Background: Immunotherapies, including immune checkpoint inhibitors (ICI), have revolutionized the treatment of many cancers, producing significant improvements in survival patients with different cancers. However, intended anti-tumor effects also result a unique form autoimmunity, known as immune-related adverse events (irAEs), which emerged limiting factor for immunotherapies. Cutaneous irAEs (cirAEs), most frequently occurring ICI–related toxicities, been associated improved efficacy...
<h3>Background</h3> IMvigor010 (NCT02450331) showed that atezolizumab reduced risk of death by approximately 40% in post-cystectomy ctDNA-positive patients.1 Whether ctDNA may predict toxicity immune checkpoint inhibition is unknown. Theoretically the lack tumor-derived suppression associated with presence cancer result more irAEs. <h3>Methods</h3> Patients high-risk muscle invasive bladder treated (n=300) vs observation (n=281) after surgical resection and available baseline assessment were...
<h3>Background</h3> Immune related adverse events (irAEs) and their associated morbidity/mortality are a key concern for patients receiving immune checkpoint inhibitors (ICIs). A prospective evaluation of the drivers irAEs in diverse pan-tumor cohort is needed to identify at greatest risk develop rational interception strategies. <h3>Methods</h3> We prospectively collected clinical data blood samples from with solid tumors single institution who received ICIs as standard care. Blood were...
Abstract Dose-limiting toxicities significantly impact the benefit/risk profile of many drugs. Whole genome sequencing (WGS) in patients receiving drugs with dose-limiting can identify therapeutic hypotheses to prevent these toxicities. Peripheral neuropathy (PN) is a common neurological toxicity chemotherapies no effective approach for prevention. We conducted meta-analysis time-to-PN using WGS data 4,900 European-ancestry chemotherapeutic agents 14 randomized controlled trials. identified...
Abstract Background Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer patients in last decade, but immune-related adverse events (irAEs) pose significant clinical challenges. Despite advances management these unique toxicities, there remains an unmet need to further characterize patient-level drivers irAEs order optimize benefit/risk balance receiving immunotherapy. Methods An individual-patient data post-hoc meta-analysis was performed using from 10,344 across...
<h3>Background</h3> Immune-mediated adverse events (imAE) commonly occur in patients treated with immune checkpoint inhibitors (ICI), and pneumonitis is known to 3 -5 % of anti-PD-1 / PD-L1 antibodies.<sup>1</sup> Most cases are grade 1 or 2 can be immunosuppression, but high-grade a minority fatal.<sup>2</sup> Since lung inflammatory phenotypes, including fibrotic idiopathic interstitial pneumonias infectious pneumonias, were associated allelic variation Human Leukocyte Antigen (HLA)...