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Thesis
Investigation of HIV-1-driven immunologic changes impacting comorbid pancreatic ductal adenocarcinoma
Master of Science (M.S.), Drexel University
Aug 2026
DOI:
https://doi.org/10.17918/00011546
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is considered one of the most lethal cancers, avoiding the actions of currently available treatments through its characteristic immune evasion, desmoplasia, and low immunogenicity. People living with human immunodeficiency virus type one (HIV-1; PLWH) have been shown to be at an increased risk of developing PDAC, coupled with an even poorer prognosis. These individuals are diagnosed at a later stage and on average ten years earlier than those that are HIV-1-negative. HIV-1's chronic immune activation, dysregulated signaling, and metabolic changes associated with antiretroviral therapy add to the already complicated treatment of PDAC, and with little accurate patient data, the patterns and exact mechanisms of their relationship are not completely understood. For this thesis, murine models were employed to model the comorbidities of PDAC and HIV-1. Utilizing EcoHIV-NDK, a genetically modified form of HIV-1 for murine tropism, as a model for chronic HIV-1 infection in combination with an orthotopic surgery model for PDAC oncogenesis, we aimed to study these mechanisms. Ultrasound imaging post-surgery allowed for analysis of PDAC development, while harvested tumors and lymph nodes were analyzed by size, cellular composition, and immune infiltration and effector functions. Initial findings point to increased tumor size in EcoHIV-infected animals. Ongoing work is being completed to support initial findings while measuring the levels of integrated provirus for further comparison of viral reservoirs and oncogenesis. Future studies will work to further characterize the immune mechanisms supporting the pro-tumor microenvironment of HIV-1 and the relationship between the comorbidities.
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Details
- Title
- Investigation of HIV-1-driven immunologic changes impacting comorbid pancreatic ductal adenocarcinoma
- Creators
- Lorelei D. Brown
- Contributors
- Jennifer L. Hope (Advisor)Michael R. Nonnemacher (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Master of Science (M.S.)
- Publisher
- Drexel University
- Number of pages
- xi, 66 pages
- Resource Type
- Thesis
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; College of Medicine; Drexel University
- Other Identifier
- 991022203659804721