Coordinated single-cell tumor microenvironment dynamics reinforce pancreatic cancer subtype.
Ki Oh, Yun Jae Yoo, Luke A Torre-Healy, Manisha Rao, Danielle Fassler, Pei Wang, Michael Caponegro, Mei Gao, Joseph Kim, Aaron Sasson, Georgios Georgakis, Scott Powers, Richard A Moffitt
Author Information
Ki Oh: Department of Biomedical Informatics, Stony Brook University, Stony Brook, NY, USA.
Yun Jae Yoo: Department of Biomedical Informatics, Stony Brook University, Stony Brook, NY, USA. ORCID
Luke A Torre-Healy: Department of Biomedical Informatics, Stony Brook University, Stony Brook, NY, USA. ORCID
Manisha Rao: Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, USA.
Danielle Fassler: Department of Biomedical Informatics, Stony Brook University, Stony Brook, NY, USA.
Pei Wang: Department of Cell Systems & Anatomy, University of Texas Health Science Center, San Antonio, TX, USA.
Michael Caponegro: Department of Pharmacology, Stony Brook University, Stony Brook, NY, USA.
Mei Gao: Department of Surgery, University of Kentucky and Markey Cancer Center, Lexington, KY, USA.
Joseph Kim: Department of Surgery, University of Kentucky and Markey Cancer Center, Lexington, KY, USA.
Aaron Sasson: Department of Surgery, Stony Brook University, Stony Brook, NY, USA.
Georgios Georgakis: Department of Surgery, Stony Brook University, Stony Brook, NY, USA.
Scott Powers: Department of Pathology, Stony Brook University, Stony Brook, NY, USA.
Richard A Moffitt: Department of Biomedical Informatics, Stony Brook University, Stony Brook, NY, USA. richard.austin.moffitt@emory.edu. ORCID
Bulk analyses of pancreatic ductal adenocarcinoma (PDAC) samples are complicated by the tumor microenvironment (TME), i.e. signals from fibroblasts, endocrine, exocrine, and immune cells. Despite this, we and others have established tumor and stroma subtypes with prognostic significance. However, understanding of underlying signals driving distinct immune and stromal landscapes is still incomplete. Here we integrate 92 single cell RNA-seq samples from seven independent studies to build a reproducible PDAC atlas with a focus on tumor-TME interdependence. Patients with activated stroma are synonymous with higher myofibroblastic and immunogenic fibroblasts, and furthermore show increased M2-like macrophages and regulatory T-cells. Contrastingly, patients with 'normal' stroma show M1-like recruitment, elevated effector and exhausted T-cells. To aid interoperability of future studies, we provide a pretrained cell type classifier and an atlas of subtype-based signaling factors that we also validate in mouse data. Ultimately, this work leverages the heterogeneity among single-cell studies to create a comprehensive view of the orchestra of signaling interactions governing PDAC.
References
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