A5058602789- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Chronic Lymphocytic Leukemia Research
- Glycosylation and Glycoproteins Research
- Pituitary Gland Disorders and Treatments
- Glioma Diagnosis and Treatment
- Colorectal Cancer Treatments and Studies
- Chemokine receptors and signaling
- Neutropenia and Cancer Infections
- Adrenal and Paraganglionic Tumors
- Cancer Research and Treatments
- Acute Myeloid Leukemia Research
- Immune Cell Function and Interaction
- Virus-based gene therapy research
- Cancer Genomics and Diagnostics
- Cancer Cells and Metastasis
- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
- Immune cells in cancer
- Diagnosis and treatment of tuberculosis
- Cytokine Signaling Pathways and Interactions
- T-cell and B-cell Immunology
- RNA modifications and cancer
Providence Portland Medical Center
2015-2024
Oregon Health & Science University
2020-2023
Bristol-Myers Squibb (Germany)
2023
Cancer Research Center
2015-2020
Oregon Research Institute
2020
Cancer Institute (WIA)
2018
University of New Mexico
2018
Society for Immunotherapy of Cancer
2015
University of Castilla-La Mancha
2011-2014
The purpose of this study was to evaluate the prognostic value Immunoscore in patients with stage III colon cancer (CC) and analyze its association effect chemotherapy on time recurrence (TTR).
Pancreatic ductal adenocarcinoma (PDAC) has traditionally been thought of as an immunologically quiescent tumor type presumably because a relatively low mutational burden (TMB) and poor responses to checkpoint blockade therapy. However, many PDAC tumors exhibit T cell inflamed phenotypes. The presence tertiary lymphoid structures (TLS) recently shown be predictive response in melanomas sarcomas, are prognostic for survival PDAC. In order more comprehensively understand immunity patients with...
Despite the success of checkpoint blockade in some cancer patients, there is an unmet need to improve outcomes. Targeting alternative pathways, such as costimulatory molecules (e.g. OX40, GITR, and 4-1BB), can enhance T cell immunity tumor-bearing hosts. Here we describe results from a phase Ib clinical trial (NCT02274155) which 17 patients with locally advanced head neck squamous carcinoma (HNSCC) received murine anti-human OX40 agonist antibody (MEDI6469) prior definitive surgical...
Evaluation of T lymphocyte frequency provides prognostic information for patients with oral squamous cell cancer (OSCC). However, the effect simultaneously evaluating and assessing suppressive elements defects in antigen-processing machinery (APM) has not been clarified. Simultaneous characterization CD3+, CD8+, FoxP3+, CD163+, PD-L1+ cells using multispectral imaging was performed on sections from 119 HPV- OSCC. Expression β2-microglobulin, MHC class I heavy chain, large multifunctional...
Tumors with low frequencies of checkpoint positive tumor-infiltrating lymphocytes (cpTIL) have a likelihood response to PD-1 blockade. We conducted prospective multicenter phase II trial intratumoral plasmid IL-12 (tavokinogene telseplasmid; "tavo") electroporation combined pembrolizumab in patients advanced melanoma cytotoxic (cpCTL).Tavo was administered intratumorally days 1, 5, and 8 every 6 weeks while (200 mg, i.v.) 3 weeks. The primary endpoint objective rate (ORR) by RECIST,...
Abstract Purpose: Pituitary adenomas are one of the most common benign neoplasms central nervous system. Although emerging evidence suggests roles for both genetic and epigenetic factors in tumorigenesis, degree to which these contribute disease remains poorly understood. Experimental Design: A multiplatform analysis was performed identify genomic epigenomic underpinnings among three major subtypes surgically resected pituitary 48 patients: growth hormone (GH)–secreting (n = 17),...
Interleukin 12 (IL-12) is a pivotal regulator of innate and adaptive immunity. We conducted prospective open-label, phase II clinical trial electroporated plasmid IL-12 in advanced melanoma patients (NCT01502293).Patients with stage III/IV were treated intratumorally encoding (tavokinogene telseplasmid; tavo), 0.5 mg/ml followed by electroporation (six pulses, 1500 V/cm) on days 1, 5, 8 every 90 the main study additional two alternative schedule exploration cohorts. Correlative analyses for...
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Background Emerging data suggest predictive biomarkers based on the spatial arrangement of cells or coexpression patterns in tissue sections will play an important role precision immuno-oncology. Multiplexed immunofluorescence (mIF) is ideally suited to such assessments. Standardization and validation end-to-end workflow that supports multisite trials clinical laboratory processes are vital. Six institutions collaborated to: (1) optimize automated six-plex assay focused PD-1/PD-L1 axis, (2)...
Abstract Purpose: Triple-negative breast cancer (TNBC) is an aggressive disease with limited therapeutic options. Antibodies targeting programmed cell death protein 1 (PD-1)/PD-1 ligand (PD-L1) have entered the landscape in TNBC, but only a minority of patients benefit. A way to reliably enhance immunogenicity, T-cell infiltration, and predict responsiveness critically needed. Patients Methods: Using mouse models we evaluate immune activation tumor intratumoral IL12 plasmid followed by...
Background: The prognostic value of Immunoscore was evaluated in Stage II/III colon cancer (CC) patients, but it remains unclear I/II, and early-stage subgroups at risk. An international Society for Immunotherapy Cancer (SITC) study the pre-defined consensus tumors from 1885 AJCC/UICC-TNM I/II CC patients Canada/USA (Cohort 1) Europe/Asia 2). METHODS: Digital-pathology is used to quantify densities CD3+ CD8+ T-lymphocyte center tumor (CT) invasive margin (IM). time recurrence (TTR) primary...
Background Approximately 50% of head and neck squamous cell carcinomas (HNSCC) recur after treatment with curative intent. Immune checkpoint inhibitors are options for recurrent/metastatic HNSCC; however, less than 20% patients respond. To increase this response rate, it is fundamental to our understanding the spatial tumor immune microenvironment (TIME). Methods In total, 53 HNSCC specimens were included. Using a seven-color multiplex immunohistochemistry panel we identified cells,...
Background: Tumor microenvironment may have a key role in providing immunological markers that can help predict clinical response to treatment with checkpoint inhibitors. We investigated whether the baseline expression of PD-L1 advanced melanoma patients treated ipilimumab correlate outcome. Methods: was assessed 114 and, cohort 77 patients, comprehensive assessment using multispectral imaging assess presence and distribution CD3+, CD8+, CD163+, FOXP3+ PD-L1+ cells inside at periphery tumor...
Abstract Background CAPRA (NCT02565992) evaluated Coxsackievirus A21 (V937) + pembrolizumab for metastatic/unresectable stage IIIB–IV melanoma. Methods Patients received intratumoral V937 on days 1, 3, 5, and 8 (then every 3 weeks [Q3W]) intravenous 2 mg/kg Q3W from day 8. Primary endpoint was safety. Results Median time first dose to data cutoff 32.0 months. No dose-limiting toxicities occurred; 14% (5/36) of patients experienced grade 3‒5 treatment-related adverse events. Objective...
Abstract Preclinical murine data indicate that fragment crystallizable (Fc)-dependent depletion of intratumoral regulatory T cells (Treg) is a major mechanism action anti–CTLA-4. However, the two main antibodies administered to patients (ipilimumab and tremelimumab) do not recapitulate these effects. Here, we investigate underlying mechanisms responsible for limited Treg observed with therapies. Using an immunocompetent model humanized CTLA-4 Fcγ receptors (FcγR), show ipilimumab...
Abstract We investigated the temporal and spatial expression of SK2 in developing mouse hippocampus using molecular biochemical techniques, quantitative immunogold electron microscopy, electrophysiology. The mRNA encoding was expressed adult hippocampus. Western blotting immunohistochemistry showed that protein increased with age. This accompanied by a shift subcellular localization. Early development (P5), predominantly localized to endoplasmic reticulum pyramidal cell layer. But P30 almost...
6011 Background: This phase Ib clinical trial was performed to investigate an agonistic murine antibody OX40 (MEDI6469) at various dose intervals prior definitive surgical resection in patients with head and neck squamous cell carcinoma (HNSCC). Methods: 17 resectable stage III-IVA HNSCC (11 = HPV-; 7 HPV+) received MEDI6469 0.4mg/kg x 3 doses administered on day 1, 3-4 5-6 of the study, followed by excision dissection either 2 days, 1 week or weeks after infusion anti-OX40. Primary tumor,...
Small-conductance, Ca(2+) -activated K(+) (SK) channels are expressed in the hippocampus where they regulate synaptic responses, plasticity, and learning memory. To investigate expression of SK3 (KCNN3) subunits, we determined developmental profile subcellular distribution developing mouse using western blots, immunohistochemistry high-resolution immunoelectron microscopy. The results showed that increased during postnatal development, localization changed from being mainly associated with...
<h3>Background</h3> One of today's greatest hurdles for cancer immunotherapy is the absence information regarding which tumor antigens are already recognized by patients receiving immunotherapies, and whether those therapies then boost or generate an immune response against proteins. For CD8+ T cells in particular, patient-specific recognition responses at level individual rarely characterized. Because this, some immunologists have turned to serum antibodies as alternative measure...