A5060460614- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Ovarian cancer diagnosis and treatment
- Cancer, Hypoxia, and Metabolism
- RNA modifications and cancer
- Immune cells in cancer
- Cancer-related molecular mechanisms research
- Lymphoma Diagnosis and Treatment
- Cutaneous lymphoproliferative disorders research
- Cytokine Signaling Pathways and Interactions
- Epigenetics and DNA Methylation
- Cancer Genomics and Diagnostics
- RNA Interference and Gene Delivery
- T-cell and B-cell Immunology
- Protein Degradation and Inhibitors
- Cancer Research and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Histone Deacetylase Inhibitors Research
- Radiomics and Machine Learning in Medical Imaging
- Immune Response and Inflammation
- Virus-based gene therapy research
- Bladder and Urothelial Cancer Treatments
- Phagocytosis and Immune Regulation
Moffitt Cancer Center
2017-2025
Duke University
2023-2025
Duke Cancer Institute
2023-2024
University of South Florida
2019-2022
University of Pennsylvania
2004-2020
Hospital of the University of Pennsylvania
2020
Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"
2019
John Wiley & Sons (United States)
2018-2019
The Wistar Institute
2010-2017
Philadelphia University
2011-2015
Although tumor-infiltrating T cells have been documented in ovarian carcinoma, a clear association with clinical outcome has not established.We performed immunohistochemical analysis of 186 frozen specimens from advanced-stage carcinomas to assess the distribution and conducted analyses. Molecular analyses were some tumors by real-time polymerase chain reaction.CD3+ detected within tumor-cell islets (intratumoral cells) 102 (54.8 percent); they undetectable 72 (38.7 remaining 12 (6.5...
Infiltrating inflammatory cells are highly prevalent within the tumor microenvironment and mediate many processes associated with progression; however, contribution of specific populations remains unclear. For example, nature function tumor-associated neutrophils (TANs) in cancer is largely unknown. The goal this study was to provide a phenotypic functional characterization TANs surgically resected lung patients. We found that constituted 5%-25% isolated from digested human tumors. Compared...
SPECIFIC AIMSThe aim of this study was to identify and characterize a novel human member the β-defensin family by screening genomic sequences, analyze its structure, tissue distribution, regulation, evaluate antimicrobial chemoattractant activities.PRINCIPAL FINDINGS1. Analysis cDNA sequences β-defensinTo around 2 at chromosomal region 8p23, peptide sequence used perform ‘basic local alignment search tool’ (BLAST) in High Throughput Genomic (HTG) division GenBank. Accession numbers AF202031,...
Chimeric antigen receptors (CAR) are synthetic molecules that provide new specificities to T cells. Although successful in treatment of hematologic malignancies, CAR cells ineffective for solid tumors date. We found the cell-surface molecule c-Met was expressed ∼50% breast tumors, prompting construction a cell specific c-Met, which halted tumor growth immune-incompetent mice with xenografts. then evaluated safety and feasibility treating metastatic cancer intratumoral administration...
Restoration of anti-tumor immunity by blocking PD-L1 signaling through the use antibodies has proven to be beneficial in cancer therapy. Here, we show that BET bromodomain inhibition suppresses expression and limits tumor progression ovarian cancer. CD274 (encoding PD-L1) is a direct target BRD4-mediated gene transcription. In mouse models, treatment with inhibitor JQ1 significantly reduced on cells tumor-associated dendritic macrophages, which correlated an increase activity cytotoxic T...
PD-L1 antibodies produce efficacious clinical responses in diverse human cancers, but the basis for their effects remains unclear, leaving a gap understanding of how to rationally leverage therapeutic activity. is widely expressed tumor cells, its contributions pathogenicity are incompletely understood. In this study, we evaluated hypothesis that exerts cell-intrinsic signals critical pathogenesis. Using RNAi methodology, attenuated murine ovarian cell line ID8agg and melanoma B16 (termed...
Abstract Purpose: We have shown that the aged microenvironment increases melanoma metastasis, and decreases response to targeted therapy, here we queried anti-PD1. Experimental Design: analyzed relationship between age, anti-PD1, prior therapy in 538 patients. used mouse models of melanoma, analyze intratumoral immune young versus mice confirmed our findings human biopsies. Results: Patients over age 60 responded more efficiently anti-PD-1, likelihood anti-PD-1 increased with even when...
We characterized the initiation and evolution of immune response against a new inducible p53-dependent model aggressive ovarian carcinoma that recapitulates leukocyte infiltrates cytokine milieu advanced human tumors. Unlike other models initiate tumors before development mature system, we detect measurable anti-tumor immunity from very early stages, which is driven by infiltrating dendritic cells (DCs) prevents steady tumor growth for prolonged periods. Coinciding with phenotypic switch in...
Abstract The role of estrogens in antitumor immunity remains poorly understood. Here, we show that estrogen signaling accelerates the progression different estrogen-insensitive tumor models by contributing to deregulated myelopoiesis both driving mobilization myeloid-derived suppressor cells (MDSC) and enhancing their intrinsic immunosuppressive activity vivo. Differences growth are dependent on blunted and, correspondingly, disappear immunodeficient hosts upon MDSC depletion....
Tumor-associated macrophages are major contributors to malignant progression and resistance immunotherapy, but the mechanisms governing their differentiation from immature myeloid precursors remain incompletely understood. In this study, we demonstrate that exosomes secreted by human mouse tumor-educated mesenchymal stem cells (MSCs) drive accelerated breast cancer inducing of monocytic myeloid-derived suppressor into highly immunosuppressive M2-polarized at tumor beds. Mechanistically,...
Abstract Most ovarian cancers are infiltrated by prognostically relevant activated T cells 1–3 , yet exhibit low response rates to immune checkpoint inhibitors 4 . Memory B cell and plasma infiltrates have previously been associated with better outcomes in cancer 5,6 but the nature functional relevance of these responses controversial. Here, using 3 independent cohorts that total comprise 534 patients high-grade serous cancer, we show robust, protective humoral dominated production...