We aim to clarify the roles of macrophages in human pancreatic ductal adenocarcinoma (PDAC) pathophysiology. To achieve this, we have utilized the GeoMx spatial transcriptomics technology (Nanostring), available at GR on the PETRA platform, to explore macrophage features based on their localization within the tumor microenvironment. We selected patient samples with both primary tumor and metastatic, which are rare since metastatic dissemination typically contraindicates surgery. However, for four patients, we gained access to matched primary and metastatic tumor samples.
From these samples, we are sampling macrophages from the tumor core and adjacent tissue to identify modulated pathways according to their specific localization within the tumor. In the GeoMx approach, we target up to three segments within regions of interest (ROIs): CK+ cells for tumor cells, CD45+ for leukocytes, and CD68+ for macrophages. These segments are used to capture and sequence transcripts from the selected populations within the ROIs. This strategy will provide us with an unprecedented resolution for analyzing PDAC macrophages.
A pilot experiment was conducted using one PDAC patient and one colorectal cancer sample to validate the pipeline, and results from the full experiment are currently pending. This innovative approach will provide valuable insights into how macrophages contribute to PDAC progression and metastasis based on their specific localization within the tumor microenvironment.
