Multiplexed Imaging Mass Cytometry Analysis Characterizes the Vascular Niche in Pancreatic Cancer
Jonathan H Sussman1,2,3, Nathalia Kim4, Samantha B Kemp1,2
1Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Cancer Research
|May 2, 2024
Summary
Pancreatic cancer (PDAC) has a unique vascular niche. Imaging mass cytometry revealed 10 cellular neighborhoods, including a CD44-macrophage-enriched vascular niche that may drive tumor growth.
Area of Science:
- Oncology
- Immunology
- Cancer Biology
Background:
- Pancreatic ductal adenocarcinoma (PDAC) is driven by tumor microenvironment interactions.
- PDAC often features a hypovascular, hypoxic environment limiting treatment efficacy.
- Understanding the spatial features of the vascular niche is crucial for PDAC research.
Purpose of the Study:
- To investigate the spatial characteristics of the vascular microenvironment in PDAC.
- To identify distinct cellular neighborhoods and their interactions within PDAC.
- To explore the role of specific cell populations, like macrophages, in shaping the PDAC niche.
Main Methods:
- Applied imaging mass cytometry with a 26-antibody panel on 35 regions from 9 PDAC patients.
- Analyzed over 140,000 single cells to distinguish major cell types.
- Evaluated cellular neighborhoods to identify distinct spatial domains.
Main Results:
- Identified 10 distinct spatial domains within PDAC, including immune-enriched and tumor-enriched environments.
- Revealed differential interactions between immune cells and the vasculature.
- Found the vascular niche closely associated with CD44-expressing macrophages possessing a proangiogenic gene signature.
Conclusions:
- PDAC exhibits significant spatial heterogeneity.
- CD44-expressing macrophages are enriched in the PDAC vascular niche.
- These macrophages may play a key role in shaping the vascular niche and influencing PDAC progression.
