Core C – Immunophenotyping Core

SUMMARY: CORE C Cachexia is a wasting syndrome that significantly contributes to the morbidity and mortality of cancer patients, especially those diagnosed with pancreatic ductal adenocarcinoma (PDAC). The overarching hypothesis of this P01 project is that the NF-κB/IL-6/STAT3 signaling axis acts as a central regulator of the macroenvironment in PDAC-induced cachexia, encompassing tumor, skeletal muscle and adipose tissues. Three projects in this P01 focus on specific components of this signaling axis integrating on the use of mouse models and patient samples. The role of the Immunophenotyping Core will be to support molecular and histological studies in the projects requiring next generation single cell sequencing (scRNA-seq) and multispectral imaging. In addition, the Immunophenotyping Core will use deep learning methods to perform the quantitation of multiplex images of immune cells to assess the function of the NF-κB/IL-6/STAT3 signaling axis in the progression of PDAC and wasting of muscle and adipose tissues in cachexia. The two specific aims of the Immunophenotyping core is to 1) Utilize multiplex immunofluorescence panels and multispectral imaging to evaluate how the NF-κB/STAT3/IL- 6 signaling axis regulates the immune architecture contributing to PDAC tumor progression and muscle and adipose wasting; and 2) Perform single-cell RNA-sequencing (scRNA-seq) to reveal functional pathways regulated by the NF-κB/STAT3/IL-6 signaling axis in the macroenvironment of murine models of PDAC-induced cachexia.