Primary and metastatic cellular landscapes in human pancreatic cancer
Recommended Citation
Steele NG, Sirihorachai VR, Elhossiny AM, Loveless IM, Kadiyala P, Bonilla M, Lasse-Opsahl EL, Vargas CS, Donahue KL, Kemp SB, Gunchick V, Shah YM, Frankel TL, Bednar F, Rao A, Allen BL, Shi J, Sahai V, Crawford HC, Carpenter ES, and Pasca di Magliano M. Primary and metastatic cellular landscapes in human pancreatic cancer. iScience 2025;28(8):113012.
Document Type
Article
Publication Date
8-15-2025
Publication Title
iScience
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is characterized by a complex tumor microenvironment (TME). We utilized single cell RNA sequencing to compare the TMEs of metastatic sites and primary tumors. We detected increased prevalence of exhausted CD8(+) T cells in metastases, as well as the enrichment of complement pathway encoding genes in immunosuppressive tumor-associated macrophages, consistent with profound immunosuppression in metastatic disease. In cancer-associated fibroblasts, we identified a unique upregulation of metabolic genes, including UPP1, in metastasis. In cancer cells, we uncovered a specific gene signature upregulated in liver metastases; this signature was present in a proportion of primary tumors in the TCGA dataset, where it correlated with worse survival. Overall, our analysis of primary and metastatic PDAC defines a "high-risk" gene signature, metabolic reprogramming, and increased immune suppression in metastasis.
PubMed ID
40703450
Volume
28
Issue
8
First Page
113012
Last Page
113012
