Single cell and spatial transcriptomics highlight the interaction of club-like cells with immunosuppressive myeloid cells in prostate cancer.

Autor:	Kiviaho A; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.; Prostate Cancer Research Center, Tampere University and TAYS Cancer Center, Tampere, Finland., Eerola SK; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.; Prostate Cancer Research Center, Tampere University and TAYS Cancer Center, Tampere, Finland., Kallio HML; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.; Prostate Cancer Research Center, Tampere University and TAYS Cancer Center, Tampere, Finland., Andersen MK; Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.; Clinic of Surgery, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway., Hoikka M; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.; Prostate Cancer Research Center, Tampere University and TAYS Cancer Center, Tampere, Finland., Tiihonen AM; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.; Prostate Cancer Research Center, Tampere University and TAYS Cancer Center, Tampere, Finland., Salonen I; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.; Prostate Cancer Research Center, Tampere University and TAYS Cancer Center, Tampere, Finland., Spotbeen X; Laboratory of Lipid Metabolism and Cancer, KU Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium.; KU Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium., Giesen A; Department of Urology, University Hospitals Leuven, Leuven, Belgium.; Department of Development and Regeneration, KU Leuven, Leuven, Belgium., Parker CTA; University College London Cancer Institute, London, UK., Taavitsainen S; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.; Prostate Cancer Research Center, Tampere University and TAYS Cancer Center, Tampere, Finland., Hantula O; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.; Prostate Cancer Research Center, Tampere University and TAYS Cancer Center, Tampere, Finland., Marttinen M; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.; Prostate Cancer Research Center, Tampere University and TAYS Cancer Center, Tampere, Finland.; European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.; European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany., Hermelo I; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.; Prostate Cancer Research Center, Tampere University and TAYS Cancer Center, Tampere, Finland., Ismail M; University College London Cancer Institute, London, UK., Midtbust E; Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.; Clinic of Surgery, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway., Wess M; Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.; Clinic of Surgery, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway., Devlies W; Department of Urology, University Hospitals Leuven, Leuven, Belgium.; Molecular Endocrinology Laboratory, Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium., Sharma A; Department of Public Health and Nursing, Norwegian University of Science and Technology (NTNU), Trondheim, Norway., Krossa S; Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.; Central staff, St. Olavs Hospital HF, 7006, Trondheim, Norway., Häkkinen T; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.; Prostate Cancer Research Center, Tampere University and TAYS Cancer Center, Tampere, Finland., Afyounian E; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.; Prostate Cancer Research Center, Tampere University and TAYS Cancer Center, Tampere, Finland., Vandereyken K; KU Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium.; Laboratory of Reproductive Genomics, Department of Human Genetics, KU Leuven, Leuven, Belgium., Kint S; KU Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium.; Laboratory of Reproductive Genomics, Department of Human Genetics, KU Leuven, Leuven, Belgium., Kesseli J; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.; Prostate Cancer Research Center, Tampere University and TAYS Cancer Center, Tampere, Finland., Tolonen T; Prostate Cancer Research Center, Tampere University and TAYS Cancer Center, Tampere, Finland.; Department of Pathology, Fimlab Laboratories, Ltd, Tampere University Hospital, Tampere, Finland., Tammela TLJ; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.; Department of Urology, Tampere University Hospital, Tampere, Finland., Viset T; Department of Pathology, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway., Størkersen Ø; Department of Pathology, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway., Giskeødegård GF; Clinic of Surgery, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.; Department of Public Health and Nursing, Norwegian University of Science and Technology (NTNU), Trondheim, Norway., Rye MB; Clinic of Surgery, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway., Murtola T; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.; Prostate Cancer Research Center, Tampere University and TAYS Cancer Center, Tampere, Finland., Erickson A; Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; ICAN-Digital Precision Cancer Medicine Flagship, Helsinki, Finland.; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK., Latonen L; Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland., Bova GS; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.; Prostate Cancer Research Center, Tampere University and TAYS Cancer Center, Tampere, Finland., Mills IG; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.; Patrick G Johnston Centre for Cancer Research, Queen's University of Belfast, Belfast, UK., Joniau S; Department of Urology, University Hospitals Leuven, Leuven, Belgium.; Department of Development and Regeneration, KU Leuven, Leuven, Belgium., Swinnen JV; Laboratory of Lipid Metabolism and Cancer, KU Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium.; KU Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium., Voet T; KU Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium.; Laboratory of Reproductive Genomics, Department of Human Genetics, KU Leuven, Leuven, Belgium., Mirtti T; Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; ICAN-Digital Precision Cancer Medicine Flagship, Helsinki, Finland.; Department of Pathology, University of Helsinki & Helsinki University Hospital, Helsinki, Finland., Attard G; University College London Cancer Institute, London, UK.; University College London Hospitals, London, UK., Claessens F; Molecular Endocrinology Laboratory, Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium., Visakorpi T; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.; Prostate Cancer Research Center, Tampere University and TAYS Cancer Center, Tampere, Finland.; Fimlab Laboratories, Ltd, Tampere University Hospital, Tampere, Finland., Rautajoki KJ; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.; Prostate Cancer Research Center, Tampere University and TAYS Cancer Center, Tampere, Finland., Tessem MB; Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.; Clinic of Surgery, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway., Urbanucci A; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland. alfonso.urbanucci@tuni.fi.; Prostate Cancer Research Center, Tampere University and TAYS Cancer Center, Tampere, Finland. alfonso.urbanucci@tuni.fi.; Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway. alfonso.urbanucci@tuni.fi., Nykter M; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland. matti.nykter@tuni.fi.; Prostate Cancer Research Center, Tampere University and TAYS Cancer Center, Tampere, Finland. matti.nykter@tuni.fi.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2024 Nov 16; Vol. 15 (1), pp. 9949. Date of Electronic Publication: 2024 Nov 16.
DOI:	10.1038/s41467-024-54364-1
Abstrakt:	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. Competing Interests: Competing interests C.T.A.P.’s employer may gain commercially from licensing data to Artera AI. G.A. received personal fees, grants, and travel support from Janssen and Astellas Pharma; personal fees or travel support from Pfizer, Novartis/AAA, Bayer Healthcare Pharmaceuticals, AstraZeneca, and Sanofi-Aventis; in addition, G.A.’s former employer, The Institute of Cancer Research, receives royalty income from abiraterone and G.A. receives a share of this income through the Institute’s Rewards to Discoverers Scheme. G.A. has received research funding (institutional) from Janssen, Astellas Pharma, and Novartis. All other authors declare no potential conflicts of interest. (© 2024. The Author(s).)
Databáze:	MEDLINE
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