Single cell analysis of cribriform prostate cancer reveals cell intrinsic and tumor microenvironmental pathways of aggressive disease

Hong Yuen Wong, Quanhu Sheng, Amanda B. Hesterberg, Sarah Croessmann, Brenda L. Rios, Khem Giri, Jorgen Jackson, Adam X. Miranda, Evan Watkins, Kerry R. Schaffer, Meredith Donahue, Elizabeth Winkler, David F. Penson, Joseph A. Smith, S. Duke Herrell, Amy N. Luckenbaugh, Daniel A. Barocas, Young J. Kim, Diana Graves, Giovanna A. Giannico, Jeffrey C. Rathmell, Ben H. Park, Jennifer B. Gordetsky and Paula J. Hurley ()
Additional contact information
Hong Yuen Wong: Vanderbilt University Medical Center
Quanhu Sheng: Vanderbilt University Medical Center
Amanda B. Hesterberg: Vanderbilt University Medical Center
Sarah Croessmann: Vanderbilt University Medical Center
Brenda L. Rios: Vanderbilt University Medical Center
Khem Giri: Vanderbilt University Medical Center
Jorgen Jackson: Vanderbilt University Medical Center
Adam X. Miranda: Vanderbilt University Medical Center
Evan Watkins: Vanderbilt University Medical Center
Kerry R. Schaffer: Vanderbilt University Medical Center
Meredith Donahue: Vanderbilt University Medical Center
Elizabeth Winkler: Vanderbilt University Medical Center
David F. Penson: Vanderbilt-Ingram Cancer Center
Joseph A. Smith: Vanderbilt University Medical Center
S. Duke Herrell: Vanderbilt University Medical Center
Amy N. Luckenbaugh: Vanderbilt University Medical Center
Daniel A. Barocas: Vanderbilt University Medical Center
Young J. Kim: Vanderbilt-Ingram Cancer Center
Diana Graves: Vanderbilt University Medical Center
Giovanna A. Giannico: Vanderbilt University Medical Center
Jeffrey C. Rathmell: Vanderbilt-Ingram Cancer Center
Ben H. Park: Vanderbilt University Medical Center
Jennifer B. Gordetsky: Vanderbilt-Ingram Cancer Center
Paula J. Hurley: Vanderbilt University Medical Center

Nature Communications, 2022, vol. 13, issue 1, 1-21

Abstract: Abstract Cribriform prostate cancer, found in both invasive cribriform carcinoma (ICC) and intraductal carcinoma (IDC), is an aggressive histological subtype that is associated with progression to lethal disease. To delineate the molecular and cellular underpinnings of ICC/IDC aggressiveness, this study examines paired ICC/IDC and benign prostate surgical samples by single-cell RNA-sequencing, TCR sequencing, and histology. ICC/IDC cancer cells express genes associated with metastasis and targets with potential for therapeutic intervention. Pathway analyses and ligand/receptor status model cellular interactions among ICC/IDC and the tumor microenvironment (TME) including JAG1/NOTCH. The ICC/IDC TME is hallmarked by increased angiogenesis and immunosuppressive fibroblasts (CTHRC1+ASPN+FAP+ENG+) along with fewer T cells, elevated T cell dysfunction, and increased C1QB+TREM2+APOE+-M2 macrophages. These findings support that cancer cell intrinsic pathways and a complex immunosuppressive TME contribute to the aggressive phenotype of ICC/IDC. These data highlight potential therapeutic opportunities to restore immune signaling in patients with ICC/IDC that may afford better outcomes.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/s41467-022-33780-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33780-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-33780-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().