A5072600812- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- Immune cells in cancer
- Peptidase Inhibition and Analysis
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Melanoma and MAPK Pathways
- Brain Metastases and Treatment
- Signaling Pathways in Disease
- Gut microbiota and health
- Cardiac Fibrosis and Remodeling
- Esophageal Cancer Research and Treatment
- Glioma Diagnosis and Treatment
- Single-cell and spatial transcriptomics
- Dermatology and Skin Diseases
- Atherosclerosis and Cardiovascular Diseases
- Dietary Effects on Health
- Lymphatic System and Diseases
- Lung Cancer Diagnosis and Treatment
The University of Texas MD Anderson Cancer Center
2017-2025
UC San Diego Health System
2022
University of California, San Diego
2021-2022
La Jolla Alcohol Research
2022
Moores Cancer Center
2022
Gut bacteria modulate the response to immune checkpoint blockade (ICB) treatment in cancer, but effect of diet and supplements on this interaction is not well studied. We assessed fecal microbiota profiles, dietary habits, commercially available probiotic supplement use melanoma patients performed parallel preclinical studies. Higher fiber was associated with significantly improved progression-free survival 128 ICB, most pronounced benefit observed sufficient intake no use. Findings were...
Immune checkpoint blockade therapy targets T cell-negative costimulatory molecules such as cytotoxic lymphocyte antigen-4 (CTLA-4) and programmed cell death-1 (PD-1). Combination anti–CTLA-4 anti–PD-1 has enhanced efficacy, but it remains unclear through what mechanisms effects are mediated. A critical question is whether combination modulates the same populations monotherapies. Using a mass cytometry-based systems approach, we comprehensively profiled response of to monotherapy plus in...
Immune checkpoint inhibitors (ICI) targeting CTLA4 or PD-1/PD-L1 have transformed cancer therapy but are associated with immune-related adverse events, including myocarditis. Here, we report a robust preclinical mouse model of ICI-associated myocarditis in which monoallelic loss Ctla4 the context complete genetic absence Pdcd1 leads to premature death approximately half mice. Premature results from myocardial infiltration by T cells and macrophages severe ECG abnormalities, closely...
Despite the promise of immune checkpoint inhibition (ICI), therapeutic responses remain limited. This raises possibility that standard care treatments delivered in concert may compromise tumor response. To address this, we employ tobacco-signature head and neck squamous cell carcinoma murine models which map tumor-draining lymphatics develop for regional lymphablation with surgery or radiation. We find eliminates ICI response, worsening overall survival repolarizing tumor- peripheral-immune...
The effects of T cell differentiation arising from immune checkpoint inhibition targeting cytotoxic lymphocyte–associated antigen 4 (CTLA-4) and programmed death protein 1 (PD-1) on the immunological memory response remain unclear. Our investigation into anti-CTLA-4 anti-PD-1 formation in mice reveals that cells generated by exhibit greater expansion, cytokine production, antitumor activity than those anti-PD-1. Notably, preserves more factor-1 (TCF-1)+ during priming, while leads to...
Abstract Distinct effects on T-cell differentiation arise from immune checkpoint inhibition targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1). However, the effect of these immunotherapies immunological memory response remains unclear. Our investigation into anti-CTLA-4 anti-PD-1 formation in mice revealed that generates a more effective antitumor than anti-PD-1. Memory T-cells arising after treatment exhibit greater expansion, cytokine production,...
Abstract Despite the promise of immune checkpoint inhibition (ICI), therapeutic responses remain limited. This raises possibility that standard care treatments delivered in concert may compromise tumor response. To address this, we employed tobacco-signature HNSCC murine models which mapped tumor-draining lymphatics and developed for regional lymphablation with surgery or radiation. Remarkably, found eliminates ICI response, significantly worsening overall survival repolarizing tumor-...
<h3>Background</h3> Despite the proven efficacy of immune checkpoint inhibitor (ICI) therapy in recurrent/metastatic setting for head and neck squamous cell carcinoma (HNSCC), clinical trials ICI combined with curative-intent therapies have yielded equivocal results [1–4]. Collectively, this highlights gaps our understanding rational oncology (IO) treatment sequencing suggests that may be disrupted by standard therapies, which necessarily compromise regional lymphatics. <h3>Methods</h3> We...
Abstract T cell costimulation is a principal mechanism by which activation regulated, but it remains unclear whether costimulatory pathways also control differentiation. This unresolved question germane to our understanding of how function controlled and has therapeutic implications in the context cancer immunotherapy. Using mass cytometry based systems approach murine models we investigated negative regulates differentiation as well activation. Unsupervised population identification reveals...
Abstract Immune checkpoint inhibition (ICI) with anti-CTLA-4 and anti-PD-1 has revolutionized oncology; however, response rates remain limited in most cancer types, highlighting the need for more effective immune oncology (IO) treatment strategies. Paradoxically, head neck squamous cell carcinoma (HNSCC), which bears a mutational burden infiltrate commensurate cancers that respond robustly to ICI, demonstrated no anti- CTLA-4 any setting or locally-advanced disease. Scrutiny of landmark...
Abstract Both anti-CTLA-4 and anti-PD-1 mediate significant response rates in cancer patients. As a hallmark of successful immunotherapies, they also durable responses that last for years. For example, mediates 22% 10-year overall survival rate, while 34% 5-year rate. Because the broader uses number patients who have tumor relapse increases. About 25% initially responded to within 24 months. However, relationship between long-term effect immunotherapies is still not clear. The goal this...
<p>2 tables and 10 figures</p>
<div>Abstract<p>Immune checkpoint inhibitors (ICI) targeting CTLA4 or PD-1/PD-L1 have transformed cancer therapy but are associated with immune-related adverse events, including myocarditis. Here, we report a robust preclinical mouse model of ICI-associated myocarditis in which monoallelic loss <i>Ctla4</i> the context complete genetic absence <i>Pdcd1</i> leads to premature death approximately half mice. Premature results from myocardial infiltration by T...
Abstract Blocking either cytotoxic T-lymphocyte antigen-4 (CTLA-4) or programmed cell death-1 (PD-1) pathway relieves the negative regulation of T-cells resulting in durable tumor rejection patients with cancer and improved survival rate. However, it remains unclear how these immunotherapies affect memory T-cell response. Here we address whether anti-CTLA-4 anti-PD-1 have different effects on T-cells. We used therapy combination irradiated vaccine mice. After re-challenge, observed that...
<p>2 tables and 10 figures</p>
Abstract Blocking either cytotoxic T-lymphocyte antigen-4 (CTLA-4) or programmed cell death-1 (PD-1) pathway results in distinct T-cell differentiation. We investigated the effects of anti-CTLA-4 and anti-PD-1 on memory formation mice. Anti-CTLA-4 generates a more potent response than anti-PD-1. Memory T-cells generated by expand at greater frequency, have cytokine production, exhibit higher antitumor activity those These cells also frequently differentiate into KLRG1+ effector CD8 during...
<div>Abstract<p>Immune checkpoint inhibitors (ICI) targeting CTLA4 or PD-1/PD-L1 have transformed cancer therapy but are associated with immune-related adverse events, including myocarditis. Here, we report a robust preclinical mouse model of ICI-associated myocarditis in which monoallelic loss <i>Ctla4</i> the context complete genetic absence <i>Pdcd1</i> leads to premature death approximately half mice. Premature results from myocardial infiltration by T...
Abstract Both anti-CTLA-4 and anti-PD-1 mediate significant response rates in cancer patients. As a hallmark of successful immunotherapies, they also durable responses that last for years. For example, mediates 22% 10-year overall survival rate, while 34% 5-year rate. Because the broader uses number patients who have tumor relapse increases. About 25% initially responded to within 24 months. However, relationship between long-term effect immunotherapies is still not clear. The goal this...