A5032279430- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Dietary Effects on Health
- T-cell and B-cell Immunology
- Adipokines, Inflammation, and Metabolic Diseases
- Immunotherapy and Immune Responses
- Adrenal Hormones and Disorders
- Hematopoietic Stem Cell Transplantation
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Viral gastroenteritis research and epidemiology
- MicroRNA in disease regulation
- Advancements in Semiconductor Devices and Circuit Design
- Immune cells in cancer
- Lung Cancer Research Studies
- SARS-CoV-2 and COVID-19 Research
- Cytomegalovirus and herpesvirus research
- Chemotherapy-induced cardiotoxicity and mitigation
- Cardiovascular Disease and Adiposity
- Cancer, Stress, Anesthesia, and Immune Response
- Metabolism, Diabetes, and Cancer
- IL-33, ST2, and ILC Pathways
- Diabetes and associated disorders
- Lung Cancer Treatments and Mutations
- Atherosclerosis and Cardiovascular Diseases
University of California, Davis
2020-2025
UC Davis Comprehensive Cancer Center
2025
UC Davis Health System
2023
Purpose Given the unmet need for novel immunotherapy in soft tissue sarcoma (STS), we sought to characterize phenotype and function of intratumoral natural killer (NK) T cells identify strategies augment tumor-infiltrating lymphocyte (TIL) function. Experimental design Using prospectively collected specimens from dogs humans with sarcomas, archived specimens, The Cancer Genome Atlas (TCGA) data, evaluated blood tumor NK cell correlated those outcome. We then assessed effects interleukin 15...
Background/Objectives: Novel mRNA vaccines have been successfully utilized to curtail the SARS-CoV-2 pandemic. However, immunology underlying CoV2 vaccinations, particularly with repeated boosting, has not properly characterized due limitations in preclinical modeling of infection/vaccinations as well constantly changing vaccine formulations. The immunoregulatory aspects involved such approaches remain unclear. Antibodies, inherent immunogenicity by VDJ gene rearrangement, potential induce...
Abstract The PD1/PDL1 axis acts as a potent immune regulator for T cells. Inhibition of the pathway has demonstrated success in context checkpoint immunotherapy, yet biological consequences long-term effects PD1 inhibition on cells remain unclear. In murine models we have observed that signaling either through genetic ablation or blockade results increased activation and function. This been vitro stimulation PD-1-/- which percentages markers including CD25, CD69, IFNγ were observed. Similar...
Abstract Chimeric antigen receptor (CAR) T cells are currently FDA-approved and provide a curative solution for patients with select B-cell malignancies in the relapsed or refractory setting. However, there have been multiple reports of long-term toxicities associated CAR cell treatment, such as second primary malignancies, highlighting importance assessing effects on host preclinical models. Since study efficacy is performed vivo xenograft mouse models, limited by xenogeneic...
Stereotactic ablative radiotherapy (SABR) is a standard-of-care for medically-inoperable-early-stage non-small cell lung cancer (NSCLC). One third of patients progress and chemotherapy rarely used in this population. We questioned if addition the immune-checkpoint-inhibitor (ICI) atezolizumab to SABR can improve outcomes. initiated multi-institutional single-arm phase I study (NCT02599454) enrolling twenty with primary endpoint maximum tolerated dose (MTD); secondary endpoints safety...
Introduction The incidence of obesity, a condition characterized by systemic chronic inflammation, has reached pandemic proportions and is poor prognostic factor in many pathologic states. However, its role on immune parameters been diverse at times contradictory. We have previously demonstrated that obesity can result what called the “obesity paradox” which results increased T cell exhaustion, but also greater efficacy checkpoint blockade cancer treatment. Methods particularly context...
Despite obesity reaching pandemic proportions, its impact on antigen-specific T cell responses is still unclear. We have recently demonstrated that results in increased expression of PD-1 cells, and checkpoint blockade targeting PD-1/PD-L1 surprisingly resulted greater clinical efficacy cancer therapy. Adverse events associated with this therapy center around autoimmune reactions. In study, we examined the priming pathogenesis using mouse model experimental encephalomyelitis (EAE), which...
The efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is limited by the occurrence acute and chronic graft- versus -host disease (GVHD). We have recently demonstrated that obesity results in exacerbated gastrointestinal GVHD both mouse models clinical outcomes due to increased pro-inflammatory cytokine responses microbiota alterations. therefore wanted delineate role various parameters obesity, adiposity, effects high-fat (HF) diet, microbiome on pathogenesis, taking...
Purpose Clinical successes using current T-cell based immunotherapies have been limited in soft tissue sarcomas (STS), while pre-clinical studies shown evidence of natural killer (NK) cell activity. Since tumor immune infiltration, especially tumor-infiltrating lymphocytes, is associated with improved survival most solid tumors, we sought to evaluate the gene expression profile and blood NK T cells, as well goal identifying potential novel targets STS. Experimental Design Using...
Bystander activation of memory T cells occurs via cytokine signaling alone in the absence cell receptor (TCR) and provides a means amplifying effector responses an antigen-nonspecific manner.While role Programmed Cell Death Protein 1 (PD-1) on antigen-specific is extensively characterized, its bystander less clear.We examined PD-1 pathway during human mouse nonantigen-specific observed that + demonstrated proliferation than activated -populations vitro.Higher proliferative were also -memory...
The thymus is the central organ involved with T-cell development and production of naïve T cells. During normal aging, undergoes marked involution, reducing output resulting in a predominance long-lived memory cells periphery. Outside systemic stress responses that induce corticosteroids (CS), or other insults such as radiation exposure, thymocyte apoptosis, transient acute thymic involution subsequent recovery occurring after cessation stimulus. Despite increasing utilization...
Immune checkpoint inhibition (ICI) has emerged as one of the most powerful tools to reverse cancer induced immune suppression. Monoclonal antibodies (mAbs) targeting programmed cell death 1/programmed ligand 1(PD-1/PD-L1) are FDA-approved and their clinical use is rapidly expanding. As opposed paradigm, which can result in significant responses toxicities, it been difficult reproduce these effects preclinically using mouse models. In large part, this due models, employ growing ex vivo...
Abstract Obesity (BMI of 30 or higher) has reached pandemic proportions in the US and continues to rise. is associated with increased cancer incidence, progression, mortality. also a meta-inflammation as well general immune suppression. However, we others have observed both preclinical models involving diet-induced obese (DIO) mice clinical outcomes, that obesity can be efficacy T cell responses following checkpoint inhibition (ICI) targeting PD-1/PDL-1 (Wang Z et al, Nat Med 2019). This...
Abstract After TCR engagement, T cells induce expression of CD25, which forms the IL2 high affinity receptor complex, concurrently with PD1, plays a down-regulatory role in activation. Cessation stimulation leads to eventual contraction cell responses. Chimeric antigen (CAR) therapy has seen increased use past decade. CAR T-cells are activated and transduced ex vivo expanded low amounts cytokines prior administration. The CD25 PD1 on at different stages process been incompletely...
Abstract TIGIT has emerged as a critical regulator of phenotype and function in mouse human NK cells with key studies showing upregulation suppresses anti-tumor responses. However, the role promoting survival received less attention. We hypothesized that exerts dual on balancing decreased activation enhanced survival. Our results showed sorted TIGIT+ TIGIT-cell subsets upregulate to near 100%, post IL-2 cytokine stimulation, suggesting TIGIT’s importance following stimulation. Sorted...
Abstract PD1/PDL1 interactions exert potent inhibitory effects on T cell responses. Inhibition of this pathway results in greater responses and is increasingly used cancer immunotherapy but the long-term PD1 inhibition activation remain unclear. We hypothesized that these gains proliferation cells over time may result loss due to apoptosis via induced death (AICD). investigated using both mouse human models activation. from wild-type or PD1−/− mice were activated vitro by a variety stimuli....
Natural killer (NK) cells are involved in innate defense against viral infection and cancer. NK can be divided into subsets based on the ability of different receptors to bind major histocompatibility (MHC) class 1 molecules, resulting differential responses upon activation a process called "licensing" or "arming." expressing that self-MHC considered licensed due an augmented effector lytic function capability compared with unlicensed subsets. However, we demonstrated instead positively...
<h3>Background</h3> Immune checkpoint inhibitors (ICIs) particularly those targeting the PD-1/PD-L1 axis have markedly impacted cancer immunotherapy resulting in significant therapeutic responses across an increasingly wide variety of cancers. While obesity is often associated as a negative prognostic indicator and outcomes, it has surprisingly been linked to greater anti-tumor efficacy survival multiple cancers following immune blockade both preclinical models clinical outcomes. Clinical...
Abstract Thymic involution (TI) occurs with aging and during stress responses, decreasing naïve T cell output. progenitor apoptosis can occur directly by corticosteroids (CS) leading to transient followed recovery. The effects of systemic immunotherapies (IT) used in cancer or immune stimulation via acute viral infection on the thymus has not been well-characterized was primary goal this study. IT treatment mice high dose IL-2 (HD IL-2) models (mouse cytomegalovirus, MCMV) all resulted rapid...