A5012037714- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Protease and Inhibitor Mechanisms
- Immune cells in cancer
- Peptidase Inhibition and Analysis
- T-cell and B-cell Immunology
- Single-cell and spatial transcriptomics
- Immune Response and Inflammation
- Galectins and Cancer Biology
- vaccines and immunoinformatics approaches
- Cancer Genomics and Diagnostics
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Virus-based gene therapy research
- Machine Learning in Bioinformatics
- NF-κB Signaling Pathways
- Cytokine Signaling Pathways and Interactions
- Retinoids in leukemia and cellular processes
- Head and Neck Cancer Studies
- Tuberculosis Research and Epidemiology
- Inflammatory Biomarkers in Disease Prognosis
- Bioinformatics and Genomic Networks
- Hepatitis B Virus Studies
- Neuroinflammation and Neurodegeneration Mechanisms
UPMC Hillman Cancer Center
2016-2025
University of Pittsburgh
2015-2025
University of Pittsburgh Medical Center
2020-2024
Data Harbor (United States)
2015
University of Kragujevac
2009-2012
Cleveland Clinic
2009
Institute of Neuroimmunology of the Slovak Academy of Sciences
2007
Head and neck squamous cell carcinoma (HNSCC) is characterized by complex relations between stromal, epithelial, immune cells within the tumor microenvironment (TME). To enable development of more efficacious therapies, we aim to study heterogeneity, signatures unique populations, cell-cell interactions non-immune populations in 6 human papillomavirus (HPV)+ 12 HPV- HNSCC patient matched peripheral blood specimens using single-cell RNA sequencing. Using this dataset 134,606 cells, show...
Head and neck squamous cell carcinomas (HNSCCs) are common malignancies caused by carcinogens, including tobacco alcohol, or infection with human papillomavirus (HPV). Immune checkpoint inhibitors targeting the programmed death 1 (PD-1) pathway effective against unresectable recurrent/metastatic HNSCC. Here, we explored safety efficacy of anti-PD-1 therapy in at-risk resectable HPV-positive HPV-negative HNSCC neoadjuvant setting.The phase I/II CheckMate 358 trial virus-associated cancers...
Regulatory T cells (Treg cells) are critical mediators of self-tolerance, but they can also limit effective anti-tumor immunity. Although under homeostasis a small fraction Treg in lymphoid organs express the putative checkpoint molecule Tim-3, this protein is expressed by much larger proportion tumor-infiltrating cells. Using mouse model that drives cell-type-specific inducible Tim-3 expression, we show expression sufficient to drive more effector-like phenotype, resulting increases...
We performed a phase 1/2 trial testing the safety, toxicity, and immune response of vaccine consisting autologous dendritic cells (DCs) transduced with replication-defective adenovirus (AdV) encoding full-length melanoma antigen MART-1/Melan-A (MART-1). This was designed to activate MART-1–specific CD8+ CD4+ T cells. Metastatic patients received 3 injections 106 or 107 DCs, delivered intradermally. Cell surface phenotype cytokine production DCs used for vaccines were tested, indicated...
Natural killer (NK) cells are innate cytotoxic and immunoregulatory lymphocytes that have a central role in anti-tumor immunity play critical mediating cellular advanced cancer immunotherapies, such as dendritic cell (DC) vaccines. Our group recently tested novel recombinant adenovirus-transduced autologous DC-based vaccine simultaneously induces T responses against three melanoma-associated antigens for melanoma patients. Here, we examine the impact of this well subsequent systemic delivery...
Background The transmembrane protein T-cell immunoglobulin and mucin-domain containing molecule 3 (TIM-3) is an immune checkpoint receptor that expressed by a variety of leukocyte subsets, particularly in the tumor microenvironment. An effective TIM-3-targeting therapy should account for multiple biological factors, including disease setting, specific cell types involved their varying sensitivities to four putative TIM-3 ligands (galectin-9, phosphatidylserine, high mobility group B1...
Immunotherapy of cancer must promote antitumor effector cells for tumor eradication as well counteract immunoregulatory mechanisms which inhibit effectors. Immunologic therapies are showing promise, including dendritic cell-(DC-) based strategies. DC highly malleable antigen-presenting can potent immunity tolerance, depending on the environmental signals received. Previously, we tested a peptide-pulsed vaccine to Alpha-fetoprotein (AFP-) specific anti-tumor in patients with hepatocellular...
Cancer vaccines are designed to promote systemic antitumor immunity and tumor eradication. vaccination may be more efficacious in combination with additional interventions that build on or amplify their effects.Based our previous clinical vitro studies, we an antigen-engineered DC vaccine trial a polyclonal CD8+ CD4+ T cell response against three shared melanoma antigens. The 35 recipients were then randomized receive one month of high-dose IFNα observation.The resulting outcomes 2 partial...
Immune checkpoint blockade (ICB) agents are prominent immunotherapies for the treatment of advanced melanoma. However, they fail to promote any durable clinical benefit in a large cohort patients. This study assessed and molecular predictors ICB response survival A retrospective analysis was performed on 210 patients treated with PD-1 or CTLA-4 inhibitors at Barretos Cancer Hospital, Brazil. PD-L1 expression by immunohistochemistry using formalin-fixed paraffin-embedded tumor tissues...
Abstract TNF is a potent promoter of carcinogenesis and potentially important target for cancer prevention. produced as functionally distinct transmembrane soluble molecules (tmTNF sTNF, respectively), but their individual roles in are unexplored. We investigated the participation tmTNF sTNF chemically induced mice. found that injection XPro1595, dominant-negative biologic (DN-TNF) specific antagonist decreased tumor incidence growth, prolonged survival 3-methylcholanthrene (MCA)–injected...
Background: Increases in expression of ADAM10 and ADAM17 genes proteins are inconsistently found cancer lesions, not validated as clinically useful biomarkers. The enzyme-specific proteolytic activities, which solely mediated by the active mature enzymes, directly reflect enzyme cellular functions might be superior biomarkers than gene or protein expressions, comprise inactive proenzymes inactivated enzymes. Methods: Using a recent modification activity matrix analysis (PrAMA) measuring...
The essential innate immunity effector cells, natural killer and dendritic express multiple plasma membrane-associated tumor necrosis factor (TNF) superfamily (TNFSF) ligands that, through simultaneous synergistic engagement, mediate anti-cancer cytotoxicity. Here, we report that circulating B mediators of adaptive humoral immunity, also this immune mechanism. We show resting human cells isolated from peripheral blood induce apoptosis of, efficiently kill a large variety leukemia solid cell...
Recombinant adenovirus-engineered dendritic cells (Ad.DC) are potent vaccines for induction of anti-viral and anti-cancer T cell immunity. The effectiveness Ad.DC may depend on the newly described ability to crosstalk with natural killer (NK) via cell-to-cell contact, mediate activation, polarization bridging innate adaptive For this interaction occur in vivo, must be able attract NK from surrounding tissues or peripheral blood. We developed a novel live mouse imaging system-based NK-cell...
Dendritic cell (DC) immunotherapy has shown a promising ability to promote anti-tumor immunity in vitro and vivo. Many trials have tested single epitopes antigens activate T specificities, often CD8+ cells only. We previously found that determinant spreading breadth of antitumor correlates with improved clinical response. Therefore, activation expansion polyclonal, multiple antigen-specific cells, as well provide cognate help from CD4+ we created an adenovirus encoding three full length...
Dendritic cells (DC) are uniquely equipped to capture, process, and present antigens from their environment. The context in which an antigen is acquired by DC helps dictate the subsequent immune response. Cancer vaccination promotes antitumor immunity directing response expressed tumors. We have tested tumor-associated alpha-fetoprotein (AFP) as immunotherapy target. majority of hepatocellular carcinomas (HCC) upregulate secrete this oncofetal antigen. To develop cancer vaccines for HCC...
Abstract Hepatocellular carcinoma (HCC) patients with reduced natural killer (NK)–cell numbers and function have been shown to a poor disease outcome. Mechanisms underlying NK-cell deficiency dysfunction in HCC remain largely unresolved. α-Fetoprotein (AFP) is an oncofetal antigen produced by HCC. Previous studies demonstrated that tumor-derived AFP (tAFP) can indirectly impair activity suppressing dendritic cell function. However, direct tAFP effect on NK cells remains unexplored. The...
It has been known for decades that the immune system can be spontaneously activated against melanoma. The presence of tumor infiltrating lymphocytes in deposits is a positive prognostic factor. Cancer vaccination includes approaches to generate, amplify, or skew antitumor immunity. To accomplish this goal, tested involve administration antigens, antigen presenting cells other modulators, direct modulation tumor. Because success checkpoint blockade depend part on an existing response, cancer...
Immune and molecular profiling of CD8 T cells patients receiving DC vaccines expressing three full-length melanoma antigens (MAs) was performed. Antigen expression levels in DCs had no significant impact on cell or clinical responses. Patients who received checkpoint blockade before vaccination higher baseline MA-specific responses but evidence for improved functional to the vaccine. showed best low PD-1 after vaccination; however, during antigen presentation by minimal PD-1high cells. Gene...
Abstract Purpose: Although T-helper (Th) epitopes have been previously reported for many tumor antigens, including MAGE-A6, the relevant HLA-DR alleles that present these peptides are expressed by only a minority of patients. The identification antigenic presented promiscuously would extend clinical utility in vaccines and immunomonitoring cancer Experimental Design: A neural network algorithm vitro sensitization assays were employed to screen candidate their immunogenicity. Results:...
A promising vaccine strategy for the treatment of cancer involves use vaccines incorporating tumor antigen-derived synthetic peptides that can be coordinately recognized by specific CD4+ and CD8+ T-cells. Previously, we reported a MAGE-A6-derived peptide (MAGE-A6172–187) its highly-immunogenic cross-reactive homolog derived from Mycoplasma penetrans HF-2 permease (HF-2216–229) are promiscuously presented multiple HLA-DR alleles to responder T-cells obtained healthy donors melanoma patients....