A5067770777- Cancer Immunotherapy and Biomarkers
- Immune cells in cancer
- RNA regulation and disease
- Immune Cell Function and Interaction
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- NF-κB Signaling Pathways
- Immunotherapy and Immune Responses
- interferon and immune responses
- Nanoplatforms for cancer theranostics
- Chemokine receptors and signaling
- MicroRNA in disease regulation
- Photodynamic Therapy Research Studies
- Axon Guidance and Neuronal Signaling
- CAR-T cell therapy research
- Phagocytosis and Immune Regulation
- Genomics, phytochemicals, and oxidative stress
- Circular RNAs in diseases
- Immune Response and Inflammation
- RNA Interference and Gene Delivery
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cytokine Signaling Pathways and Interactions
- Cancer Cells and Metastasis
- Apelin-related biomedical research
- Glioma Diagnosis and Treatment
National Institutes of Health
2015-2024
Center for Cancer Research
2024
National Cancer Institute
2024
National Institute on Deafness and Other Communication Disorders
2015-2023
Vaccinex (United States)
2019
Emory University
2019
University of Minnesota
2019
University of California, Los Angeles
2019
John Wiley & Sons (United States)
2019
Hudson Institute
2019
Abstract Purpose: Natural killer (NK)-cell–based immunotherapy may overcome obstacles to effective T-cell–based such as the presence of genomic alterations in IFN response genes and antigen presentation machinery. All approaches be abrogated by an immunosuppressive tumor microenvironment present many solid types, including head neck squamous cell carcinoma (HNSCC). Here, we studied role myeloid-derived suppressor cells (MDSC) suppressing NK-cell function HNSCC. Experimental Design: The...
Recruitment of myeloid-derived suppressor cells (MDSCs) into tumors induces local immunosuppression in carcinomas. Here, we assessed whether SX-682, an orally bioavailable small-molecule inhibitor CXCR1 and CXCR2, could block tumor MDSC recruitment enhance T cell activation antitumor immunity following multiple forms immunotherapy. CXCR2+ neutrophilic MDSCs (PMN-MDSCs) were the most abundant myeloid subset within oral lung syngeneic PMN-MDSCs demonstrated greater suppression...
Checkpoint inhibitors are relatively inefficacious in head and neck cancers, despite an abundance of genetic alterations a T-cell-inflamed phenotype. One significant barrier to efficacy may be the recruitment myeloid-derived suppressor cells (MDSC) into tumor microenvironment. Here we demonstrate functional inhibition MDSC with IPI-145, inhibitor PI3Kδ PI3Kγ isoforms, which enhances responses PD-L1 blockade. Combination therapy induced CD8
Patients with head and neck squamous cell carcinoma harbor T cell-inflamed non-T tumors. Despite this, only 20% of patients respond to checkpoint inhibitor immunotherapy. Lack induction innate immunity through pattern-recognition receptors, such as the stimulator interferon (IFN) genes (STING) receptor, may represent a significant barrier development effective antitumor immunity. Here, we demonstrate robust control (MOC1), but not (MOC2), model cancer by activation STING pathway synthetic...
Abstract Near-infrared photoimmunotherapy (NIR-PIT) induces immunogenic cell death but has mostly failed to induce durable antitumor responses in syngenic tumor mouse models. We hypothesized that adaptive immune resistance could be limiting after treatmemt with NIR-PIT. investigated the effects of combining NIR-PIT targeting cell-surface CD44 and PD-1 blockade multiple syngeneic In two three models, monotherapy halted growth, enhanced dendritic infiltration, induced de novo antigen–specific...
Preclinical evidence suggests that high-dose hypofractionated ionizing radiation (IR) can enhance anti-tumor immunity and result in significant tumor control when combined with immune checkpoint blockade (ICB). However, low-dose daily fractioned IR used for many types including head neck squamous cell carcinoma results lymphopenia may be immunosuppressive. We compared correlates, primary abscopal rates following the addition of PD-1 mAb to either hypofractioned (8Gyx2) or fractionated...
Abstract Purpose: To identify deregulated and inhibitory miRNAs generate novel mimics for replacement nanomedicine head neck squamous cell carcinomas (HNSCC). Experimental Design: We integrated miRNA mRNA expression, copy number variation, DNA methylation results from The Cancer Genome Atlas (TCGA), with a functional genome-wide screen. Results: reveal that the miR-30 family is commonly repressed, all 5 members sharing these seed sequence similarly inhibit HNSCC proliferation in vitro....
Local immunosuppression remains a critical problem that limits clinically meaningful response to checkpoint inhibition in patients with head and neck cancer. Here, we assessed the impact of MDSC elimination on responses CTLA-4 inhibition.Murine syngeneic carcinoma immune infiltrates were characterized by flow cytometry. Granulocytic MDSCs (gMDSCs) depleted T-lymphocyte antigen-specific measured. Tumor-bearing mice treated depletion blockade. Immune signatures within human HNSCC datasets from...
Surgical resection of primary tumor with regional lymphadenectomy remains the treatment choice for patients advanced human papillomavirus-negative head and neck squamous cell carcinoma. However, even when pathologic disease-free margins can be achieved, locoregional and/or distant disease relapse high. Perioperative immunotherapy may improve outcomes, but mechanistic data supporting use neoadjuvant or adjuvant clinically are sparse.Two syngeneic models oral cavity carcinoma defined T-cell...
Checkpoint inhibitors targeting the PD-1/PD-L1 axis are promising immunotherapies shown to elicit objective responses against multiple tumor types, yet these agents fail benefit most patients with carcinomas. This highlights need develop effective therapeutic strategies increase blockade. Histone deacetylase (HDAC) in combination have provided preliminary evidence of anti-tumor effects. We investigated here whether exposure either natural killer (NK) cells and/or two different classes HDAC...
Intrinsic resistance to cytotoxic T-lymphocyte (CTL) killing limits responses immune activating anti-cancer therapies. Here, we established that activation of the G2/M cell cycle checkpoint results in tumor pause and protection from granzyme B-induced death. This was reversed with WEE1 kinase inhibition, leading enhanced CTL antigen-positive cells. Similarly, but at a later time point, following TNFα exposure transmembrane TNFα-dependent induction apoptosis necroptosis bystander...
Tumor infiltration by immunosuppressive myeloid cells, such as myeloid-derived suppressor cells (MDSCs), causes resistance to immunotherapy. Semaphorin4D, originally characterized for its axonal guidance properties, also contributes endothelial cell migration and survival modulates global immune cytokine profiles polarization within the tumor microenvironment. Here, we show how a therapeutic murine Sema4D mAb improves responses immune-checkpoint blockade (ICB) in two carcinoma models....
Recurrent respiratory papillomatosis (RRP) is a human papillomavirus (HPV)-driven disorder that causes substantial morbidity and can lead to fatal distal airway obstruction post-obstructive pneumonias. Patients require frequent surgical debridement of disease, no approved systemic adjuvant therapies exist.A phase II study was conducted investigate the clinical activity safety programmed death-ligand 1 (PD-L1) blockade with avelumab in patients RRP.Twelve were treated. All laryngeal RRP...
Failed T cell-based immunotherapies in the presence of genomic alterations antigen presentations pathways may be overcome by NK immunotherapy. This approach still limited immunosuppressive myeloid populations. Here, we demonstrate that cells (haNKs) engineered to express a PD-L1 chimeric receptor (CAR) haNKs killed panel human and murine head neck cancer at low effector-to-target ratios PD-L1-dependent fashion. Treatment syngeneic tumors resulted CD8 tumor rejection or growth inhibition...
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