A5002862559- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Lymphoma Diagnosis and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Chronic Lymphocytic Leukemia Research
- Cancer Immunotherapy and Biomarkers
- Single-cell and spatial transcriptomics
- Immunodeficiency and Autoimmune Disorders
- Immune Cell Function and Interaction
- SARS-CoV-2 and COVID-19 Research
- Virus-based gene therapy research
- Protease and Inhibitor Mechanisms
- Cancer Genomics and Diagnostics
- Viral-associated cancers and disorders
- Peptidase Inhibition and Analysis
- Glycosylation and Glycoproteins Research
- vaccines and immunoinformatics approaches
- Immune cells in cancer
- Cell Adhesion Molecules Research
- PARP inhibition in cancer therapy
- Enzyme Production and Characterization
- RNA Interference and Gene Delivery
- Nuclear Receptors and Signaling
- T-cell and B-cell Immunology
- Multiple and Secondary Primary Cancers
Oregon Health & Science University
2022-2025
Stanford University
2017-2023
Stanford Medicine
2017-2022
Stratford University
2019
Memorial Sloan Kettering Cancer Center
2010-2011
Kettering University
2010
University of Ottawa
2002
Innate immune cells can constitute a substantial proportion of the within tumor microenvironment and have been associated with malignancy in patients animal models cancer; however, mechanisms by which they modulate cancer progression are incompletely understood. Here, we show that high levels cathepsin protease activity induced majority macrophages pancreatic islet cancers, mammary tumors, lung metastases during malignant progression. We further tumor-associated macrophage (TAM)-supplied...
The microenvironment is known to critically modulate tumor progression, yet its role in regulating treatment response poorly understood. Here we found increased macrophage infiltration and cathepsin protease levels mammary tumors following paclitaxel (Taxol) chemotherapy. Cathepsin-expressing macrophages protected against Taxol-induced cell death coculture, an effect fully reversed by inhibition mediated partially cathepsins B S. Macrophages were also protect induced additional...
Abstract To obtain a deeper understanding of poor responses to COVID-19 vaccination in patients with lymphoma, we assessed blocking antibodies, total anti-spike IgG, and spike-specific memory B cells the peripheral blood 126 lymphoma 20 age-matched healthy controls 1 4 months after vaccination. Fifty-five percent developed antibodies postvaccination, compared 100% controls. When evaluating last treated from days nearly 18 years prior vaccination, time since anti-CD20 was significant...
Accumulating evidence suggests that apoptotic and inflammatory factors contribute to the demise of dopaminergic neurons. In this respect, Fas, a member tumor necrosis factor receptor family with proapoptotic functions, was reported be elevated within striatum substantia nigra pars compacta (SNc) Parkinson's disease (PD) patients. Accordingly, present investigation evaluated function Fas in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model PD. Injection MPTP increased nigral...
Antitumor T cell responses are the primary mediators of cancer immunotherapy. However, many other components immune system needed for efficient to be generated. Here, we developed a combinatorial approach where Toll-like receptor 9 agonist (CpG) and Fc-fused IL-12 protein were injected together into just one several tumor sites in mouse. This combination led body-wide (abscopal) therapeutic multiple models. These systemic dependent not only on cells but also B cells. activated by treatment...
Abstract Purpose: Activating T cell costimulatory receptors is a promising approach for cancer immunotherapy. In preclinical work, adding an OX40 agonist to in situ vaccination (ISV) with SD101, TLR9 agonist, was curative mouse model of lymphoma. We sought test this combination Phase I clinical trial patients low-grade B Patients and Methods: treated 14 low-dose radiation, intratumoral intravenous BMS986178, agonistic anti-OX40 antibody. The primary outcome safety. Secondary outcomes...
<p>Supplementary Figure 5. Intratumoral T cell subsets are differentially activated by treatment.</p>
<p>Supplementary Figure 6. Treatment did not alter TGF-beta in tumors.</p>
<p>Supplementary Figure 2. Assay for measuring OX40 saturation; Abundance and expression of T cell subsets.</p>
<p>Supplementary Figure 3. Tumor B cells were identified by phenotypic clustering and restricted light chain expression.</p>
<p>Supplementary Figure 1. Coformulation of SD-101 and BMS-986178 does not alter their properties; Distant target lesions show variable response.</p>
<p>Supplementary Figure 4. Flow cytometry T cell gating and proportion of Tregs.</p>
<div>AbstractPurpose:<p>Activating T-cell costimulatory receptors is a promising approach for cancer immunotherapy. In preclinical work, adding an OX40 agonist to <i>in situ</i> vaccination with SD101, TLR9 agonist, was curative in mouse model of lymphoma. We sought test this combination phase I clinical trial patients low-grade B-cell lymphoma.</p>Patients and Methods:<p>We treated 14 low-dose radiation, intratumoral intravenous BMS986178, agonistic...
<p>Supplementary Figure 7. OX40 expression did not increase after SD101 (CpG) injection in a similar prior trial.</p>
The variable clinical course of follicular lymphoma (FL) is determined by the molecular heterogeneity tumor cells and complex interactions within microenvironment (TME). IL-4 producing helper T (TFH) are critical components FL TME. Binding to IL-4R on activates JAK/STAT signaling. We identified STAT6 mutations (STAT6MUT) in 13% (N = 33/258), all clustered DNA binding domain. Gene expression data immunohistochemistry showed upregulation IL-4/STAT6 target genes STAT6MUT FL, including CCL17,...
Therapeutic advances for diffuse large B-cell lymphoma (DLBCL) have led to an increasing number of survivors. Both DLBCL and its treatments perturb the immune system, yet little is known about health during extended survivorship.
DNA damage, an important initiator of neuronal death, has been implicated in numerous neurodegenerative conditions. We previously delineated several pathways that control embryonic cortical death evoked by the DNA-damaging agent, camptothecin. In this model, tumor suppressor p53 and cyclin-dependent kinases (CDKs) are activated independently cooperate to mediate conserved pathway. To further our understanding, we presently examined whether c-Jun/JNK pathway modulates is regulated CDKs, p53,...
Abstract In this proof-of-concept study, we developed a single-cell method that provides genotypes of somatic alterations found in coding regions messenger RNAs and integrates these transcript-based variants with their matching cell transcriptomes. We used nanopore adaptive sampling on complementary DNA libraries to validate target gene transcripts, short-read sequencing characterize types harboring the mutations. CRISPR edits for 16 targets were identified using cancer line, known line...