The Role of IL-23 in Pancreatic Tumor Microenvironment
Year: 2025
Type: dissertation
Abstract: IL-12 family cytokines are an attractive therapeutic candidate for generating anti-tumor immune responses due to their stimulatory role in both innate and adaptive immunity. Preliminary data from our group has shown IL12b-dependent tumor differentiation where orthotopic pancreatic cancer in IL12b-/- mice results in poorly differentiated tumor morphology. Indeed, patients with low levels of IL12b exhibit tumor desmoplasia and have worse outcomes. Previous results have showed that tumors in the IL12b (p40) mice display poorly differentiated morphology which leads to more severe outcomes in human populations along with increased desmoplasia in pancreatic cancer and rich tumor microenvironment. The role of immune modulators in driving tumor morphology in PDAC (Pancreatic ductal adenocarcinoma) is poorly understood. PDAC is characterized by significant desmoplasia. We find that low expression levels of cytokine IL23 in patients with PDAC correlate with poor differentiation status. Consistent with these observations, we have found loss of host derived IL23 in our mouse model of PDAC leads to an altered tumor morphology appearing to be less differentiated. Single cell RNA sequencing revealed fibroblasts are enriched for IL23 receptors to evaluate changes across the tumor microenvironment with loss of IL-12 and IL23. One cell type that expresses the receptors necessary to respond to IL23 is fibroblasts. Here we evaluate the changes in fibrosis across genotypes using color deconvolution.
DOI: 10.17615/chd7-se94
Author: Choi, Grace
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W6944033575
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