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

doi:10.1038/s41467-024-54364-1

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 KrossaTomi 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

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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.

Original language	English
Article number	9949
Journal	Nature Communications
Volume	15
DOIs	https://doi.org/10.1038/s41467-024-54364-1
Publication status	Published - 16 Nov 2024

Bibliographical note

Keywords

Humans
Male
Tumor Microenvironment/immunology
Single-Cell Analysis
Prostatic Neoplasms/genetics
Transcriptome
Myeloid Cells/metabolism
Myeloid-Derived Suppressor Cells/metabolism
Prostate/metabolism
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Epithelial Cells/metabolism
Androgens/metabolism

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41467-024-54364-1Licence: CC BY

Single cell and spatial transcriptomics highlight the interaction of club-like cells with immunosuppressive myeloid cells in prostate cancer
Copyright 2024 the authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Final published version, 4.24 MBLicence: CC BY

Cite this

Kiviaho, A., Eerola, S. K., Kallio, H. M. L., Andersen, M. K., Hoikka, M., Tiihonen, A. M., Salonen, I., Spotbeen, X., Giesen, A., Parker, C. T. A., Taavitsainen, S., Hantula, O., Marttinen, M., Hermelo, I., Ismail, M., Midtbust, E., Wess, M., Devlies, W., Sharma, A., ... Nykter, M. (2024). Single cell and spatial transcriptomics highlight the interaction of club-like cells with immunosuppressive myeloid cells in prostate cancer. Nature Communications, 15, Article 9949. https://doi.org/10.1038/s41467-024-54364-1

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title = "Single cell and spatial transcriptomics highlight the interaction of club-like cells with immunosuppressive myeloid cells in prostate cancer",

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.",

keywords = "Humans, Male, Tumor Microenvironment/immunology, Single-Cell Analysis, Prostatic Neoplasms/genetics, Transcriptome, Myeloid Cells/metabolism, Myeloid-Derived Suppressor Cells/metabolism, Prostate/metabolism, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Epithelial Cells/metabolism, Androgens/metabolism",

author = "Antti Kiviaho and Eerola, {Sini K} and Kallio, {Heini M L} and Andersen, {Maria K} and Miina Hoikka and Tiihonen, {Aliisa M} and Iida Salonen and Xander Spotbeen and Alexander Giesen and Parker, {Charles T A} and Sinja Taavitsainen and Olli Hantula and Mikael Marttinen and Isma{\"i}l Hermelo and Mazlina Ismail and Elise Midtbust and Maximilian Wess and Wout Devlies and Abhibhav Sharma and Sebastian Krossa and Tomi H{\"a}kkinen and Ebrahim Afyounian and Katy Vandereyken and Sam Kint and Juha Kesseli and Teemu Tolonen and Tammela, {Teuvo L J} and Trond Viset and {\O}ystein St{\o}rkersen and Giske{\o}deg{\aa}rd, {Guro F} and Rye, {Morten B} and Teemu Murtola and Andrew Erickson and Leena Latonen and Bova, {G Steven} and Mills, {Ian G} and Steven Joniau and Swinnen, {Johannes V} and Thierry Voet and Tuomas Mirtti and Gerhardt Attard and Frank Claessens and Tapio Visakorpi and Rautajoki, {Kirsi J} and May-Britt Tessem and Alfonso Urbanucci and Matti Nykter",

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year = "2024",

month = nov,

day = "16",

doi = "10.1038/s41467-024-54364-1",

language = "English",

volume = "15",

journal = "Nature Communications",

issn = "2041-1723",

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Kiviaho, A, Eerola, SK, Kallio, HML, Andersen, MK, Hoikka, M, Tiihonen, AM, Salonen, I, Spotbeen, X, Giesen, A, Parker, CTA, Taavitsainen, S, Hantula, O, Marttinen, M, Hermelo, I, Ismail, M, Midtbust, E, Wess, M, Devlies, W, Sharma, A, Krossa, S, Häkkinen, T, Afyounian, E, Vandereyken, K, Kint, S, Kesseli, J, Tolonen, T, Tammela, TLJ, Viset, T, Størkersen, Ø, Giskeødegård, GF, Rye, MB, Murtola, T, Erickson, A, Latonen, L, Bova, GS, Mills, IG, Joniau, S, Swinnen, JV, Voet, T, Mirtti, T, Attard, G, Claessens, F, Visakorpi, T, Rautajoki, KJ, Tessem, M-B, Urbanucci, A & Nykter, M 2024, 'Single cell and spatial transcriptomics highlight the interaction of club-like cells with immunosuppressive myeloid cells in prostate cancer', Nature Communications, vol. 15, 9949. https://doi.org/10.1038/s41467-024-54364-1

TY - JOUR

T1 - Single cell and spatial transcriptomics highlight the interaction of club-like cells with immunosuppressive myeloid cells in prostate cancer

AU - Kiviaho, Antti

AU - Eerola, Sini K

AU - Kallio, Heini M L

AU - Andersen, Maria K

AU - Hoikka, Miina

AU - Tiihonen, Aliisa M

AU - Salonen, Iida

AU - Spotbeen, Xander

AU - Giesen, Alexander

AU - Parker, Charles T A

AU - Taavitsainen, Sinja

AU - Hantula, Olli

AU - Marttinen, Mikael

AU - Hermelo, Ismaïl

AU - Ismail, Mazlina

AU - Midtbust, Elise

AU - Wess, Maximilian

AU - Devlies, Wout

AU - Sharma, Abhibhav

AU - Krossa, Sebastian

AU - Häkkinen, Tomi

AU - Afyounian, Ebrahim

AU - Vandereyken, Katy

AU - Kint, Sam

AU - Kesseli, Juha

AU - Tolonen, Teemu

AU - Tammela, Teuvo L J

AU - Viset, Trond

AU - Størkersen, Øystein

AU - Giskeødegård, Guro F

AU - Rye, Morten B

AU - Murtola, Teemu

AU - Erickson, Andrew

AU - Latonen, Leena

AU - Bova, G Steven

AU - Mills, Ian G

AU - Joniau, Steven

AU - Swinnen, Johannes V

AU - Voet, Thierry

AU - Mirtti, Tuomas

AU - Attard, Gerhardt

AU - Claessens, Frank

AU - Visakorpi, Tapio

AU - Rautajoki, Kirsi J

AU - Tessem, May-Britt

AU - Urbanucci, Alfonso

AU - Nykter, Matti

PY - 2024/11/16

Y1 - 2024/11/16

N2 - 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.

AB - 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.

KW - Humans

KW - Male

KW - Tumor Microenvironment/immunology

KW - Single-Cell Analysis

KW - Prostatic Neoplasms/genetics

KW - Transcriptome

KW - Myeloid Cells/metabolism

KW - Myeloid-Derived Suppressor Cells/metabolism

KW - Prostate/metabolism

KW - Gene Expression Profiling

KW - Gene Expression Regulation, Neoplastic

KW - Epithelial Cells/metabolism

KW - Androgens/metabolism

U2 - 10.1038/s41467-024-54364-1

DO - 10.1038/s41467-024-54364-1

M3 - Article

C2 - 39550375

SN - 2041-1723

VL - 15

JO - Nature Communications

JF - Nature Communications

M1 - 9949

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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