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 () and Matti Nykter ()
Additional contact information
Antti Kiviaho: Tampere University
Sini K. Eerola: Tampere University
Heini M. L. Kallio: Tampere University
Maria K. Andersen: Norwegian University of Science and Technology
Miina Hoikka: Tampere University
Aliisa M. Tiihonen: Tampere University
Iida Salonen: Tampere University
Xander Spotbeen: KU Leuven and Leuven Cancer Institute (LKI)
Alexander Giesen: University Hospitals Leuven
Charles T. A. Parker: University College London Cancer Institute
Sinja Taavitsainen: Tampere University
Olli Hantula: Tampere University
Mikael Marttinen: Tampere University
Ismaïl Hermelo: Tampere University
Mazlina Ismail: University College London Cancer Institute
Elise Midtbust: Norwegian University of Science and Technology
Maximilian Wess: Norwegian University of Science and Technology
Wout Devlies: University Hospitals Leuven
Abhibhav Sharma: Norwegian University of Science and Technology (NTNU)
Sebastian Krossa: Norwegian University of Science and Technology
Tomi Häkkinen: Tampere University
Ebrahim Afyounian: Tampere University
Katy Vandereyken: KU Leuven
Sam Kint: KU Leuven
Juha Kesseli: Tampere University
Teemu Tolonen: Tampere University and TAYS Cancer Center
Teuvo L. J. Tammela: Tampere University
Trond Viset: Trondheim University Hospital
Øystein Størkersen: Trondheim University Hospital
Guro F. Giskeødegård: Trondheim University Hospital
Morten B. Rye: Trondheim University Hospital
Teemu Murtola: Tampere University
Andrew Erickson: University of Helsinki
Leena Latonen: University of Eastern Finland
G. Steven Bova: Tampere University
Ian G. Mills: University of Oxford
Steven Joniau: University Hospitals Leuven
Johannes V. Swinnen: KU Leuven and Leuven Cancer Institute (LKI)
Thierry Voet: KU Leuven
Tuomas Mirtti: University of Helsinki
Gerhardt Attard: University College London Cancer Institute
Frank Claessens: KU Leuven
Tapio Visakorpi: Tampere University
Kirsi J. Rautajoki: Tampere University
May-Britt Tessem: Norwegian University of Science and Technology
Alfonso Urbanucci: Tampere University
Matti Nykter: Tampere University

Nature Communications, 2024, vol. 15, issue 1, 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.

Date: 2024
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DOI: 10.1038/s41467-024-54364-1

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