A5009860570- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Immune cells in cancer
- Immune Cell Function and Interaction
- Single-cell and spatial transcriptomics
- Dietary Effects on Health
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Cancer Research and Treatments
- Pancreatic and Hepatic Oncology Research
- Hepatocellular Carcinoma Treatment and Prognosis
- Cancer, Stress, Anesthesia, and Immune Response
- Chemokine receptors and signaling
- Cancer Genomics and Diagnostics
- Immunodeficiency and Autoimmune Disorders
- Inflammatory mediators and NSAID effects
- Cancer Cells and Metastasis
- Ferroptosis and cancer prognosis
- Cardiovascular Disease and Adiposity
- Cancer, Hypoxia, and Metabolism
- Renal cell carcinoma treatment
- Cell Image Analysis Techniques
- Multiple and Secondary Primary Cancers
- Diet and metabolism studies
- Colorectal Cancer Treatments and Studies
Johns Hopkins University
2022-2025
Sidney Kimmel Comprehensive Cancer Center
2022-2025
Johns Hopkins Medicine
2023-2025
University of Baltimore
2023-2024
Bloomberg (United States)
2022
The treatment of hepatocellular carcinoma (HCC) has been transformed by the use immune checkpoint inhibitors. However, most patients with HCC do not benefit from immunotherapy. There is an urgent need to understand mechanisms that underlie response or resistance immunotherapy for HCC. syngeneic mouse models closely recapitulate heterogeneity human will provide opportunities examine complex interactions between cancer cells and nonmalignant in tumor microenvironment.
BACKGROUNDImmune-related adverse events (irAEs) and their associated morbidity/mortality are a key concern for patients receiving immune checkpoint inhibitors (ICIs). Prospective evaluation of the drivers irAEs in diverse pan-tumor cohort is needed to identify at greatest risk develop rational treatment interception strategies.METHODSIn an observational study, we prospectively collected blood samples performed regular clinical evaluations ICI therapy as standard care solid tumors. We...
Neoadjuvant immunotherapy is thought to produce long-term remissions through induction of antitumor immune responses before removal the primary tumor. Tertiary lymphoid structures (TLS), germinal center-like that can arise within tumors, may contribute establishment immunological memory in this setting, but understanding their role remains limited. Here, we investigated contribution TLS immunity hepatocellular carcinoma (HCC) treated with neoadjuvant immunotherapy. We found induced formation...
Background Obesity is a risk factor for developing cancer but also associated with improved outcomes after treatment immune checkpoint inhibitors (ICIs), phenomenon called the obesity paradox. To interrogate mechanisms of divergent responses in obese and non-obese patients, we examined relationship among status, clinical responses, profiles from diverse, pan-tumor cohort patients treated ICI-based therapy. Methods From June 2021 to March 2023, prospectively collected serial peripheral blood...
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)...
Abstract Most new cancer diagnoses occur in patients over the age of 65. The composition and function immune system changes with age, but how aged affects responses to checkpoint inhibitor (ICI) therapies remains incompletely understood. Here, using multiplex cytokine assay high-parameter mass cytometry, we analyze prospectively collected blood samples from 104 receiving ICIs. We find ( ≥ 65-years-old; n = 54) derive similar clinical outcomes as younger 50). However, aged, compared young,...
Abstract Recent approvals of immune checkpoint inhibitor (ICI) based regimens have transformed the clinical landscape advanced hepatocellular carcinoma (HCC), however, responses are only observed in a minority patients. Trimethylamine-N-oxide (TMAO) is an amine oxide biosynthesized from trimethylamine (TMA), generated when gut bacteria metabolize dietary choline via enzyme CutC. While prior studies shown that TMAO concentrations positively correlate with risk several gastrointestinal...
Abstract Background: Despite the recent success of immune checkpoint inhibitor (ICI) based regimens in advanced stage HCC, clinical outcomes remain poor with a median overall survival (OS) under two years. There is an unmet need to improve responses to, and durability of, ICI therapy HCC. IL-8 chemokine promoting attraction myeloid cells via receptor CXCR1/2 has been shown have numerous pro-tumorigenic roles tumor microenviroment (TiME). Recent work by others that high plasma concentration...
e16309 Background: The optimal management of BR-PDAC remains undefined due to the high rate local progression and/or metastasis with upfront surgery alone. Given limited activity single agent PD-1 blockade in PDAC, combination strategies aimed at increasing high-avidity T-cells tumor microenvironment (TME) are under investigation. GVAX is an allogenic, whole cell, GM-CSF-secreting vaccine that activates T-cell immunity against tumor-associated antigens. Prior work has shown low-dose...
Techniques for robust immune profiling of mouse tumor and blood are key to understanding immunological responses in models cancer. Here, we describe mass cytometry (cytometry by time-of-flight) procedures facilitate high-parameter low-volume survival samples end-of-study samples. We employ live-cell barcoding systems mark all cells from each improve cost-effectiveness minimize batch effects. For complete details on the use execution this protocol, please refer Charmsaz et al. (2021).1.
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...
Abstract Background: Chronic systemic inflammation mediated by pro-inflammatory cytokines serves as a major mechanism which obesity contributes to cancer development. Paradoxically, elevated body mass (BMI) has been associated with improved outcomes after treatment immune checkpoint inhibitors (ICIs) in many tumor types. The interplay between cytokine response and ICIs is poorly understood. To characterize underlying mechanisms, we investigated profiles relation clinical patients treated...
Abstract Despite the advent of immune checkpoint inhibitors (ICI) that have markedly changed treatment landscape for select tumors, pancreatic ductal adenocarcinoma (PDAC) remains unresponsive to such an approach. Features PDAC tumor microenvironment contribute resistance, including influence cancer-associated fibroblasts (CAF) on and cells, remain poorly understood. Antigen-presenting CAFs (apCAFs) express MHC-II activate CD4 T cells in genetically engineered mouse models, but are rarely...
Abstract Immunotherapies that modulate T cell function have been firmly established in cancer immunotherapy, whereas the potential for B cells antitumor immune response is not as well understood. cell-activating factor (BAFF) a cytokine belonging to TNF ligand family activates and linked autoimmunity. Our preliminary research has identified BAFF target enhancing immunity through presentation of tumor neoantigens inducing tertiary lymphoid structures which can orchestrate tumor-specific...
Abstract Background: Tertiary lymphoid structures (TLS) are ectopic follicles that arise in non-lymphoid tissue. TLS may contribute to response immune checkpoint blockade (ICB) solid tumors, but understanding of the life cycle these structures, particularly circumstances their resolution and functional contribution this stage adaptive response, remains incomplete. Methods: We employed a multi-omics approach evaluate tumors patients with hepatocellular carcinoma (HCC) treated neoadjuvant ICB...
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...
4547 Background: ICI combinations (combos) in the form of dual or plus tyrosine kinase inhibitors (TKI) combos currently represent most effective therapies mRCC patients (pts). However, there is an unmet need to discover biomarkers predictive clinical benefit combos. Circulating cytokines are important regulators immune system and may contribute cancer immunotherapy outcomes. In mRCC, prior studies showed that baseline expression influences outcomes monotherapy, but this association unknown...
Abstract Fibrolamellar hepatocellular carcinoma (FLC) is a rare and often lethal form of liver cancer that primarily affects children young adults. A fusion between DNAJB1, heat shock chaperone protein, PRKACA, the catalytic domain protein kinase (PKA) has been identified as signature genomic event in FLC, but effect this on tumor immune microenvironment not understood. We created an orthotopic, syngeneic model FLC (TIBx-FLC) by inducing DNAJB1-PRKACA murine hepatoblastoma-derived cell line...
<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...