Nature Communications (Nov 2024)
Single cell and spatial transcriptomics highlight the interaction of club-like cells with immunosuppressive myeloid cells in prostate cancer
- Antti Kiviaho,
- Sini K. Eerola,
- Heini M. L. Kallio,
- Maria K. Andersen,
- Miina Hoikka,
- Aliisa M. Tiihonen,
- Iida Salonen,
- Xander Spotbeen,
- Alexander Giesen,
- Charles T. A. Parker,
- Sinja Taavitsainen,
- Olli Hantula,
- Mikael Marttinen,
- Ismaïl Hermelo,
- Mazlina Ismail,
- Elise Midtbust,
- Maximilian Wess,
- Wout Devlies,
- Abhibhav Sharma,
- Sebastian Krossa,
- Tomi Häkkinen,
- Ebrahim Afyounian,
- Katy Vandereyken,
- Sam Kint,
- Juha Kesseli,
- Teemu Tolonen,
- Teuvo L. J. Tammela,
- Trond Viset,
- Øystein Størkersen,
- Guro F. Giskeødegård,
- Morten B. Rye,
- Teemu Murtola,
- Andrew Erickson,
- Leena Latonen,
- G. Steven Bova,
- Ian G. Mills,
- Steven Joniau,
- Johannes V. Swinnen,
- Thierry Voet,
- Tuomas Mirtti,
- Gerhardt Attard,
- Frank Claessens,
- Tapio Visakorpi,
- Kirsi J. Rautajoki,
- May-Britt Tessem,
- Alfonso Urbanucci,
- Matti Nykter
Affiliations
- Antti Kiviaho
- Faculty of Medicine and Health Technology, Tampere University
- Sini K. Eerola
- Faculty of Medicine and Health Technology, Tampere University
- Heini M. L. Kallio
- Faculty of Medicine and Health Technology, Tampere University
- Maria K. Andersen
- Department of Circulation and Medical Imaging, Norwegian University of Science and Technology
- Miina Hoikka
- Faculty of Medicine and Health Technology, Tampere University
- Aliisa M. Tiihonen
- Faculty of Medicine and Health Technology, Tampere University
- Iida Salonen
- Faculty of Medicine and Health Technology, Tampere University
- Xander Spotbeen
- Laboratory of Lipid Metabolism and Cancer, KU Leuven and Leuven Cancer Institute (LKI)
- Alexander Giesen
- Department of Urology, University Hospitals Leuven
- Charles T. A. Parker
- University College London Cancer Institute
- Sinja Taavitsainen
- Faculty of Medicine and Health Technology, Tampere University
- Olli Hantula
- Faculty of Medicine and Health Technology, Tampere University
- Mikael Marttinen
- Faculty of Medicine and Health Technology, Tampere University
- Ismaïl Hermelo
- Faculty of Medicine and Health Technology, Tampere University
- Mazlina Ismail
- University College London Cancer Institute
- Elise Midtbust
- Department of Circulation and Medical Imaging, Norwegian University of Science and Technology
- Maximilian Wess
- Department of Circulation and Medical Imaging, Norwegian University of Science and Technology
- Wout Devlies
- Department of Urology, University Hospitals Leuven
- Abhibhav Sharma
- Department of Public Health and Nursing, Norwegian University of Science and Technology (NTNU)
- Sebastian Krossa
- Department of Circulation and Medical Imaging, Norwegian University of Science and Technology
- Tomi Häkkinen
- Faculty of Medicine and Health Technology, Tampere University
- Ebrahim Afyounian
- Faculty of Medicine and Health Technology, Tampere University
- Katy Vandereyken
- KU Leuven Institute for Single Cell Omics (LISCO), KU Leuven
- Sam Kint
- KU Leuven Institute for Single Cell Omics (LISCO), KU Leuven
- Juha Kesseli
- Faculty of Medicine and Health Technology, Tampere University
- Teemu Tolonen
- Prostate Cancer Research Center, Tampere University and TAYS Cancer Center
- Teuvo L. J. Tammela
- Faculty of Medicine and Health Technology, Tampere University
- Trond Viset
- Department of Pathology, St. Olav’s Hospital, Trondheim University Hospital
- Øystein Størkersen
- Department of Pathology, St. Olav’s Hospital, Trondheim University Hospital
- Guro F. Giskeødegård
- Clinic of Surgery, St. Olavs Hospital, Trondheim University Hospital
- Morten B. Rye
- Clinic of Surgery, St. Olavs Hospital, Trondheim University Hospital
- Teemu Murtola
- Faculty of Medicine and Health Technology, Tampere University
- Andrew Erickson
- Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki
- Leena Latonen
- Institute of Biomedicine, University of Eastern Finland
- G. Steven Bova
- Faculty of Medicine and Health Technology, Tampere University
- Ian G. Mills
- Nuffield Department of Surgical Sciences, University of Oxford
- Steven Joniau
- Department of Urology, University Hospitals Leuven
- Johannes V. Swinnen
- Laboratory of Lipid Metabolism and Cancer, KU Leuven and Leuven Cancer Institute (LKI)
- Thierry Voet
- KU Leuven Institute for Single Cell Omics (LISCO), KU Leuven
- Tuomas Mirtti
- Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki
- Gerhardt Attard
- University College London Cancer Institute
- Frank Claessens
- Molecular Endocrinology Laboratory, Cellular and Molecular Medicine, KU Leuven
- Tapio Visakorpi
- Faculty of Medicine and Health Technology, Tampere University
- Kirsi J. Rautajoki
- Faculty of Medicine and Health Technology, Tampere University
- May-Britt Tessem
- Department of Circulation and Medical Imaging, Norwegian University of Science and Technology
- Alfonso Urbanucci
- Faculty of Medicine and Health Technology, Tampere University
- Matti Nykter
- Faculty of Medicine and Health Technology, Tampere University
- DOI
- https://doi.org/10.1038/s41467-024-54364-1
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 16
Abstract
Abstract Prostate cancer treatment resistance is a significant challenge facing the field. Genomic and transcriptomic profiling have partially elucidated the mechanisms through which cancer cells escape treatment, but their relation toward the tumor microenvironment (TME) remains elusive. Here we present a comprehensive transcriptomic landscape of the prostate TME at multiple points in the standard treatment timeline employing single-cell RNA-sequencing and spatial transcriptomics data from 120 patients. We identify club-like cells as a key epithelial cell subtype that acts as an interface between the prostate and the immune system. Tissue areas enriched with club-like cells have depleted androgen signaling and upregulated expression of luminal progenitor cell markers. Club-like cells display a senescence-associated secretory phenotype and their presence is linked to increased polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC) activity. Our results indicate that club-like cells are associated with myeloid inflammation previously linked to androgen deprivation therapy resistance, providing a rationale for their therapeutic targeting.
