Medicine and Health Sciences Commons^™

Withaferin A And Immune Checkpoint Blocker Therapy For The Treatment Of Non-Small Cell Lung Cancer, Roukiah Khalil

USF Tampa Graduate Theses and Dissertations

Lung cancer is the first cause of cancer-related deaths in both men and women with an overall five-year survival rate of 28%. Although immune checkpoint blockers (ICBs) are currently FDA-approved for the treatment of non-small cell lung cancer (NSCLC), only 17-20% of patients achieve durable responses by the induction of immunologic memory. The lack of response in most patients can be attributed to the tumor-intrinsic or tumor-extrinsic immune resistance mechanisms. A biomarker of importance is the Programmed Death Ligand-1 (PD-L1), as higher PD-L1 expression is usually associated with a better response to ICBs. Although studies have attempted to combine ICBs …

Role Of Hla-Drb1 Fucosylation In Anti-Melanoma Immunity, Daniel K. Lester

USF Tampa Graduate Theses and Dissertations

Melanoma is the one of the most lethal skin malignancies due to its ability to rapidly metastasize and evade the immune system. One factor that influences melanoma’s ability to metastasize and evade the immune system is the tumor microenvironment. The tumor microenvironment is a complex ecosystem that consists of melanoma cells interacting with different proteins and cell types such as cytokines, extra cellular matrix proteins, and various immune cells. While different immune cells can have various implications in the tumor microenvironment, some tumor infiltrating lymphocytes (TIL) have the potential to suppress these tumors. Recent therapeutic strategies aim to enhance TILs …

Determining The Role Of Dendritic Cells During Response To Treatment With Paclitaxel/Anti-Tim-3, Alycia Gardner

USF Tampa Graduate Theses and Dissertations

Intratumoral CD103+ dendritic cells (cDC1) are required for anti-tumor immune responses. In tumors that are poorly responsive to immunotherapeutic approaches targeting T cells, targeting cDC1 represents an alternative approach that may be useful in improving patient response rates. As such, it is critical to understand cDC1 function within tumors, and what may be preventing optimal function of cDC1. TIM-3 is a receptor that is highly expressed by cDC1 in murine and human mammary tumors, and TIM-3 blocking antibodies are currently being evaluated in clinical trials for a number of solid and hematological malignancies. In order to best design combinatorial therapeutic …

Observational Study Of Talimogene Laherparepvec Use In The Anti-Pd-1 Era For Melanoma In The Us (Cosmus-2), James Sun, Brian R. Gastman, Lucy Mccahon, Elizabeth I. Buchbinder, Igor Puzanov, Michele Nanni, James M. Lewis, Richard D. Carvajal, Shahnaz Singh-Kandah, Anupam M. Desai, Leon Raskin, Carrie M. Nielson, Rubina Ismail, Jonathan S. Zager

Oncologic Sciences Faculty Publications

Aim: Talimogene laherparepvec (T-VEC) is an intralesional therapy for unresectable, metastatic melanoma. T-VEC real-world use in the context of anti-PD1-based therapy requires further characterization.

Materials & methods: A retrospective review of T-VEC use from 1 January 2017 and 31 March 2018 for melanoma patients was conducted at seven US institutions.

Results: Among 83 patients, three categories of T-VEC and anti-PD-1 therapy were identified: T-VEC used without anti-PD-1 (n = 29, 35%), T-VEC after anti-PD-1-based therapy (n = 22, 27%) and concurrent T-VEC and anti-PD-1-based therapy (n = 32, 39%). 25% of patients discontinued T-VEC therapy due to no remaining injectable …

Microfluidic Biopsy Trapping Device For The Real-Time Monitoring Of The Tumor Microenvironment, Angela Holton

USF Tampa Graduate Theses and Dissertations

The tumor microenvironment is composed of cellular and stromal components such as tumor cells, mesenchymal cells, immune cells, cancer associated fibroblasts and the supporting extracellular matrix. The tumor microenvironment provides crucial support for growth and progression of tumor cells and affects tumor response to therapeutic interventions. To better understand tumor biology and to develop effective cancer therapeutic agents it is important to develop preclinical platforms that can faithfully recapitulate the tumor microenvironment and the complex interaction between the tumor and its surrounding stromal elements. Drug studies performed in vitro with conventional two-dimensional cancer cell line models do not optimally represent …

Diverse Inflammatory Responses In Transgenic Mouse Models Of Alzheimer's Disease And The Effect Of Immunotherapy On These Responses, Donna M. Wilcock, Qun Zhao, Dave Morgan, Marcia N. Gordon, Angela Everhart, Joan G. Wilson, Jennifer E. Lee, Carol A. Colton

Molecular Pharmacology & Physiology Faculty Publications

While the presence of an inflammatory response in AD (Alzheimer's disease) is well known, the data on inflammation are conflicting, suggesting that inflammation either attenuates pathology, exacerbates it or has no effect. Our goal was to more fully characterize the inflammatory response in APP (amyloid precursor protein) transgenic mice with and without disease progression. In addition, we have examined how anti-Aβ (amyloid β-peptide) immunotherapy alters this inflammatory response. We have used quantitative RT–PCR (reverse transcription–PCR) and protein analysis to measure inflammatory responses ranging from proinflammatory to anti-inflammatory and repair factors in transgenic mice that develop amyloid deposits only …