Multiplexed Imaging Mass Cytometry Analysis Characterizes the Vascular Niche in Pancreatic Cancer.

Autor:	Sussman JH; Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania.; Graduate Group in Genomics and Computational Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Kim N; Department of Biomedical and Molecular Sciences, School of Computing, Queen's University, Kingston, Canada., Kemp SB; Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania., Traum D; Department of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania., Katsuda T; Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania., Kahn BM; Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania., Xu J; Graduate Group in Genomics and Computational Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Kim IK; Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania., Eskandarian C; Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania., Delman D; Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Beatty GL; Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Kaestner KH; Department of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania., Simpson AL; Department of Biomedical and Molecular Sciences, School of Computing, Queen's University, Kingston, Canada., Stanger BZ; Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania.
Jazyk:	angličtina
Zdroj:	Cancer research [Cancer Res] 2024 Jul 15; Vol. 84 (14), pp. 2364-2376.
DOI:	10.1158/0008-5472.CAN-23-2352
Abstrakt:	Oncogenesis and progression of pancreatic ductal adenocarcinoma (PDAC) are driven by complex interactions between the neoplastic component and the tumor microenvironment, which includes immune, stromal, and parenchymal cells. In particular, most PDACs are characterized by a hypovascular and hypoxic environment that alters tumor cell behavior and limits the efficacy of chemotherapy and immunotherapy. Characterization of the spatial features of the vascular niche could advance our understanding of inter- and intratumoral heterogeneity in PDAC. In this study, we investigated the vascular microenvironment of PDAC by applying imaging mass cytometry using a 26-antibody panel on 35 regions of interest across 9 patients, capturing more than 140,000 single cells. The approach distinguished major cell types, including multiple populations of lymphoid and myeloid cells, endocrine cells, ductal cells, stromal cells, and endothelial cells. Evaluation of cellular neighborhoods identified 10 distinct spatial domains, including multiple immune and tumor-enriched environments as well as the vascular niche. Focused analysis revealed differential interactions between immune populations and the vasculature and identified distinct spatial domains wherein tumor cell proliferation occurs. Importantly, the vascular niche was closely associated with a population of CD44-expressing macrophages enriched for a proangiogenic gene signature. Taken together, this study provides insights into the spatial heterogeneity of PDAC and suggests a role for CD44-expressing macrophages in shaping the vascular niche. Significance: Imaging mass cytometry revealed that pancreatic ductal cancers are composed of 10 distinct cellular neighborhoods, including a vascular niche enriched for macrophages expressing high levels of CD44 and a proangiogenic gene signature. (©2024 American Association for Cancer Research.)
Databáze:	MEDLINE
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