A5049823792- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- interferon and immune responses
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Circular RNAs in diseases
- RNA modifications and cancer
- Immune cells in cancer
- Phagocytosis and Immune Regulation
- Reproductive System and Pregnancy
- Inflammasome and immune disorders
- Cell death mechanisms and regulation
- NF-κB Signaling Pathways
- Cancer Research and Treatments
- Polyomavirus and related diseases
- Breastfeeding Practices and Influences
- GDF15 and Related Biomarkers
- Effects of Radiation Exposure
- Neonatal Respiratory Health Research
- Epigenetics and DNA Methylation
- COVID-19 Impact on Reproduction
- T-cell and B-cell Immunology
- RNA Interference and Gene Delivery
- Cancer, Stress, Anesthesia, and Immune Response
- CRISPR and Genetic Engineering
University of Pennsylvania
2023
National Institute on Deafness and Other Communication Disorders
2017-2021
National Institutes of Health
2017-2021
National Center for Tumor Diseases
2019
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...
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...
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...
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...
<h3>Background</h3> Natural killer (NK) cells recognize and lyse target tumor in an MHC-unrestricted fashion complement antigen- MHC-restricted killing by T-lymphocytes. NK T-lymphocytes mediate early of targets through a common granzyme B-dependent mechanism. Tumor cell resistance to B how this alters is not clearly defined. <h3>Methods</h3> sensitivity cultured murine KIL human high affinity (haNK) the presence or absence AZD1775, small molecule inhibitor WEE1 kinase, was assessed via real...
Tumor cells activate the G2/M cell cycle checkpoint in response to ionizing radiation (IR) and effector immune cell-derived granzyme B facilitate repair survival. Wee1 kinase inhibition reverses ability of tumor pause at G2/M. Here, we hypothesized that AZD1775, a small molecule inhibitor kinase, could sensitize IR T-lymphocyte killing improve responses combination programmed death (PD)-axis blockade (ICB). Multiple models head neck carcinoma, lung carcinoma melanoma were used vitro vivo...
Loss or mutation of TP53 has been linked to alterations in anti-tumor immunity as well dysregulation cell cycle and apoptosis. We explored immunologic effects mechanisms following restoration wild-type human cDNA murine oral cancer cells using the therapeutic nanocomplex scL-53. demonstrated scL-53 induces dose-dependent expression induction apoptosis immunogenic death. further both TP53-dependent independent tumor immunogenicity through use blocking mAbs, loaded with DNA plasmid without...
Abstract Head and neck squamous cell carcinomas (HNSCC) induced by human papillomavirus (HPV) have increased recently in the US. However, distinct alterations of molecules involved death pathways drug effects targeting inhibitor apoptosis proteins (IAPs) not been extensively characterized HPV(+) HNSCC cells. In this study, we observed genomic expression nine genes 55% tissues, which were associated with HPV status, tumor staging, anatomic locations. Expression four was statistically...
Abstract Antigen-specific elimination of tumor cells by cytotoxic T-lymphocytes (CTL) inherently relies upon the sensitivity target to effector products such as granzyme B, TNFa, TNF-related apoptosis-inducing ligand (TRAIL), and Fas (FasL). Cell cycle progression is critically required for B TNF superfamily-induced apoptosis. Thus, we hypothesized that inhibition Wee1 with AZD1775 would release G2/M cell checkpoint enhance oral cavity cancer CTL killing. To explore this hypothesis, stably...
<p>Supplemental data not critical for the main conclusions of work but important review data.</p>
<p>Supplemental data not critical for the main conclusions of work but important review data.</p>
<div>AbstractPurpose:<p>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.</p>Experimental...
<div>AbstractPurpose:<p>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.</p>Experimental...
Abstract Breastfeeding has long been associated with health benefits for the infant. Breast milk is composed of essential nutrients and bioactive molecules shaping growth, immune development offspring. An optimal mammary gland (MG) during pregnancy critical to maintaining beneficial effects lactation. Nevertheless, how lactation process regulated by system remains largely unexplored. Our data reveal that commitment epithelial cells into milk-secreting accumulation T-bet +lymphoid cells,...
Abstract Pregnancy presents a challenging immunological dilemma. The maternal immune system must tolerate fetal antigens, which implies pregnancy may induce specific mechanisms of immunoregulation. Yet within this regulatory milieu, protection against pathogens be maintained. How does the navigate these opposing demands? Successfully navigating dilemma is essential for supporting reproductive fitness organism, and generally, survival any mammalian species. Of particular importance in context...
Abstract Head and neck squamous cell carcinomas (HNSCC) induced by human papilloma virus (HPV) have increased recently in the US, exhibit a different prognosis response to therapies from HPV(-) cancers. Analysis of HNSCC TCGA datasets provide evidence for distinct alterations expression components NF-κB death pathways with HPV status. Previously, we found that birinipant, novel SMAC mimetic inhibits inhibitor apoptosis proteins (IAPs), sensitizes subset lines agonists like TNF-α TRAIL. In...
Abstract Head and neck squamous cell carcinomas (HNSCC) induced by human papilloma virus (HPV) have increased recently in the US. Analysis of HNSCC TCGA datasets provide evidence for distinct alterations expression NF-κB components death pathways HPV(+) HNSCC. Previously, we found that Birinapant, a novel SMAC mimetic inhibits inhibitor apoptosis proteins (IAPs), exhibits single agent activity sensitizes subset HPV(-) lines to agonists like TNF-α TRAIL. Birinapant exhibited anti-tumor...
Abstract Human papilloma virus positive (HPV+) head and neck squamous cell carcinomas (HNSCC) exhibit a better prognosis response to therapies than HPV(-) cancers. Analysis of HNSCC TCGA dataset provides evidence for distinct alterations in expression components the NF-κB death pathways HPV(+/-) HNSCC. Previously, we have found that birinapant, novel SMAC mimetic inhibits inhibitor apoptosis proteins (IAPs), sensitizes subset lines agonists like TNF-α TRAIL. In our current study, observed...