A5057995830- Cancer Immunotherapy and Biomarkers
- Head and Neck Cancer Studies
- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Ear and Head Tumors
- Salivary Gland Tumors Diagnosis and Treatment
- Cancer Diagnosis and Treatment
- Immune cells in cancer
- Lung Cancer Research Studies
- RNA Interference and Gene Delivery
- Lung Cancer Treatments and Mutations
- Tumors and Oncological Cases
- Head and Neck Surgical Oncology
- Peptidase Inhibition and Analysis
- Cervical Cancer and HPV Research
- Chemokine receptors and signaling
- interferon and immune responses
- Cell death mechanisms and regulation
- Brain Metastases and Treatment
- Reconstructive Surgery and Microvascular Techniques
- Cancer, Lipids, and Metabolism
- Voice and Speech Disorders
- RNA modifications and cancer
- Hearing, Cochlea, Tinnitus, Genetics
Emory University
2020-2025
University of Atlanta
2024
University of Pittsburgh
2014-2024
Winship Cancer Institute
2024
Cancer Institute (WIA)
2024
Emory and Henry College
2021-2022
National Institute on Deafness and Other Communication Disorders
2015-2021
Johns Hopkins University
2015-2021
Johns Hopkins Medicine
2016-2021
National Institutes of Health
2015-2020
Programmed Death 1 (PD-1) and T cell Ig mucin domain-3 protein (Tim-3) are immune checkpoint receptors that expressed on tumor-infiltrating lymphocytes (TIL) in tumor-bearing mice humans. As anti-PD-1 single agent response rates only <20% head neck squamous carcinoma (HNSCC) patients, it is important to understand how multiple inhibitory maintain suppressed cellular immunity. One such receptor, Tim-3, activates downstream proliferative pathways through Akt/S6, highly dysfunctional TIL. We...
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...
Improved understanding of expression immune checkpoint receptors (ICR) on tumor-infiltrating lymphocytes (TIL) may facilitate more effective immunotherapy in head and neck cancer (HNC) patients. A higher frequency PD-1+ TIL has been reported human papillomavirus (HPV)+ HNC patients, despite the role PD-1 T-cell exhaustion. This discordance led us to hypothesize that extent accurately defines function prognostic impact, because PD-1high T cells be exhausted than PD-1low influence clinical...
Background Anti-PD-1 immune checkpoint blockade is approved for first-line treatment of recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), but few patients respond. Statin drugs (HMG-CoA reductase inhibitors) are associated with superior survival in several cancer types, including HNSCC. Emerging data suggest that manipulation cholesterol may enhance some aspects antitumor immunity. Methods We used syngeneic murine models (mouse oral cancer, MOC1 TC-1) to investigate our...
Abstract Head and neck squamous cell carcinoma (HNSCC) has been treated for decades with cisplatin chemotherapy, anti–PD-1 immunotherapy recently approved the treatment of this disease. However, preclinical studies how antitumor immunity in HNSCC is affected by alone or combination immunotherapies are lacking. Here, we show that sublethal doses may enhance antigen presentation T-cell killing vitro, though also upregulates tumor expression PD-L1 impair function at higher doses. In a syngeneic...
BACKGROUNDCisplatin is widely used to treat adult and pediatric cancers. It the most ototoxic drug in clinical use, resulting permanent hearing loss approximately 50% of treated patients. There a major need for therapies that prevent cisplatin-induced loss. Studies mice suggest concurrent use statins reduces loss.METHODSWe examined thresholds from 277 adults with cisplatin head neck cancer. Pretreatment posttreatment audiograms were collected within 90 days initiation completion therapy. The...
Evidence supports short courses of perioperative antibiotics for patients receiving minor head and neck procedures. Few studies have addressed antibiotic prophylaxis undergoing free flap reconstruction defects.To determine ideal in reconstruction.Retrospective cohort study 427 adults defects at 2 affiliated tertiary care academic hospitals between January 1, 2006, 28, 2013.Prophylactic type duration were recorded from patient records.Outcome data abstracted patients' medical records...
Human papillomavirus 16 (HPV16) E6 antibodies may be an early marker of the diagnosis and recurrence human papillomavirus-driven oropharyngeal cancer (HPV-OPC).This study identified 161 incident (OPC) cases diagnosed at University Pittsburgh (2003-2013) with pretreatment serum. One hundred twelve had preexisting clinical HPV testing p16 immunohistochemistry in situ hybridization (87 were dual-positive [HPV-OPC], 25 dual-negative [HPV-negative]); 62 least 1 posttreatment serum sample....
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...
Cisplatin is a chemotherapy drug that frequently causes auditory impairment due to the death of mechanosensory hair cells. ototoxicity may result from oxidative stress, DNA damage, and inflammatory cytokines. The transcription factor STAT1, an important mediator cell death, can regulate all these processes in other types. We used cultured utricles mature Swiss Webster mice investigate role STAT1 cisplatin-induced death. show phosphorylation early event both cells support after exposure...
Head and neck squamous cell carcinomas (HNSCCs) frequently harbor genomic mutations in death pathways. Nearly 30% of HNSCCs overexpress Fas-Associated Death Domain (FADD), with or without BIRC2/3 genes encoding cellular Inhibitor Apoptosis Proteins 1/2 (cIAP1/2), critical components the Tumor Necrosis Factor (TNF) Receptor signaling ASTX660 is a novel non-peptidomimetic antagonist cIAP1/2 XIAP under evaluation clinical trial for advanced solid tumors lymphomas. Herein, we show that ASTX660,...
Abstract Background While T cell-activating immunotherapies against recurrent head and neck squamous cell carcinoma (HNSCC) have shown impressive results in clinical trials, they are often ineffective the majority of patients. NK cells potential targets for immunotherapeutic intervention; however, setback monalizumab-based therapy HNSCC highlights need an alternative treatment to enhance their antitumor activity. Methods Single-cell RNA sequencing (scRNA-seq) TCGA datasets were used identify...
Programmed Death 1 (PD-1) and T cell Ig mucin domain-3 protein (Tim-3) are immune checkpoint receptors highly expressed on tumor infiltrating lymphocytes (TIL). PD-1 inhibits activation type-1 responses, while Tim-3 is proposed to mark more extensively exhausted cells, although the mechanisms underlying function not clear. Trials of anti-PD-1 therapy have identified a large subset non-responder patients, likely due expression alternative molecules like Tim-3. We investigated phenotypic...
ABSTRACT The role of T cell receptor (TCR) signaling for adaptive immune responses is essential. ability to respond a broad spectrum tumor antigens requires an selection various TCR. So far, little known about the TCR richness and clonality in cellular response head neck cancer (HNC), though Endothelial Growth Factor Receptor (EGFR)-specific CD8+ can be enhanced by cetuximab therapy. Therefore, we investigated differences sequences between human papillomavirus (HPV)+ HPV− HNC patients, as...
Inhibitor of apoptosis protein (IAP) antagonists have shown activity in preclinical models head and neck squamous cell carcinoma (HNSCC), work across several cancer types has demonstrated diverse immune stimulatory effects including enhancement T cell, NK dendritic function. However, tumor-cell-intrinsic mechanisms for this upregulation been largely unexplored. In study, we show that ASTX660, an antagonist cIAP1/2 XIAP, induces expression immunogenic death (ICD) markers sensitive HNSCC lines...
Abstract Purpose: The combination of pembrolizumab (a PD-1 inhibitor) and cabozantinib VEGF has shown promising disease control in recurrent or metastatic head neck cancer (rmHNC). Building on previous research linking plasma metabolites to weight loss, clinical outcomes, survival HNC patients standard therapy, this study evaluates pre- post-treatment as indicators therapeutic response treated with therapy. Methods: In a phase II single-arm trial rmHNC patients, blood was collected before 9...
Statin drugs, frequently used to treat hyperlipidemia, are associated with improved survival outcomes in multiple solid tumor types, including head and neck squamous cell carcinoma (HNSCC). Preclinical studies suggest that manipulation of cholesterol statins other agents can enhance the function components involved anti-tumor immune responses. Retrospective types statin therapy is responses checkpoint blockade (ICB), but this has not yet been investigated HNSCC. Pharmacy records were...