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IL-23 secreted by myeloid cells drives castration-resistant prostate cancer

Author

Listed:
  • Arianna Calcinotto

    (Oncology Institute of Southern Switzerland)

  • Clarissa Spataro

    (Oncology Institute of Southern Switzerland)

  • Elena Zagato

    (Oncology Institute of Southern Switzerland)

  • Diletta Di Mitri

    (Oncology Institute of Southern Switzerland)

  • Veronica Gil

    (The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust)

  • Mateus Crespo

    (The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust)

  • Gaston De Bernardis

    (Oncology Institute of Southern Switzerland)

  • Marco Losa

    (Oncology Institute of Southern Switzerland)

  • Michela Mirenda

    (Oncology Institute of Southern Switzerland)

  • Emiliano Pasquini

    (Oncology Institute of Southern Switzerland)

  • Andrea Rinaldi

    (Oncology Institute of Southern Switzerland)

  • Semini Sumanasuriya

    (The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust)

  • Maryou B. Lambros

    (The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust)

  • Antje Neeb

    (The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust)

  • Roberta Lucianò

    (URI, IRCCS Ospedale San Raffaele)

  • Carlo A. Bravi

    (URI, IRCCS Ospedale San Raffaele)

  • Daniel Nava-Rodrigues

    (The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust)

  • David Dolling

    (The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust)

  • Tommaso Prayer-Galetti

    (University of Padova)

  • Ana Ferreira

    (The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust)

  • Alberto Briganti

    (URI, IRCCS Ospedale San Raffaele)

  • Antonio Esposito

    (San Raffaele Scientific Institute)

  • Simon Barry

    (IMED Oncology AstraZeneca, Li Ka Shing Centre)

  • Wei Yuan

    (The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust)

  • Adam Sharp

    (The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust)

  • Johann de Bono

    (The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust)

  • Andrea Alimonti

    (Oncology Institute of Southern Switzerland
    Università della Svizzera italiana, Faculty of Biomedical Sciences
    University of Lausanne UNIL
    University of Padova)

Abstract

Patients with prostate cancer frequently show resistance to androgen-deprivation therapy, a condition known as castration-resistant prostate cancer (CRPC). Acquiring a better understanding of the mechanisms that control the development of CRPC remains an unmet clinical need. The well-established dependency of cancer cells on the tumour microenvironment indicates that the microenvironment might control the emergence of CRPC. Here we identify IL-23 produced by myeloid-derived suppressor cells (MDSCs) as a driver of CRPC in mice and patients with CRPC. Mechanistically, IL-23 secreted by MDSCs can activate the androgen receptor pathway in prostate tumour cells, promoting cell survival and proliferation in androgen-deprived conditions. Intra-tumour MDSC infiltration and IL-23 concentration are increased in blood and tumour samples from patients with CRPC. Antibody-mediated inactivation of IL-23 restored sensitivity to androgen-deprivation therapy in mice. Taken together, these results reveal that MDSCs promote CRPC by acting in a non-cell autonomous manner. Treatments that block IL-23 can oppose MDSC-mediated resistance to castration in prostate cancer and synergize with standard therapies.

Suggested Citation

  • Arianna Calcinotto & Clarissa Spataro & Elena Zagato & Diletta Di Mitri & Veronica Gil & Mateus Crespo & Gaston De Bernardis & Marco Losa & Michela Mirenda & Emiliano Pasquini & Andrea Rinaldi & Semin, 2018. "IL-23 secreted by myeloid cells drives castration-resistant prostate cancer," Nature, Nature, vol. 559(7714), pages 363-369, July.
    • Handle: RePEc:nat:nature:v:559:y:2018:i:7714:d:10.1038_s41586-018-0266-0
    DOI: 10.1038/s41586-018-0266-0
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    Citations

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    Cited by:

    1. Shunsuke Tsuzuki & Shotaro Nakanishi & Mitsuyoshi Tamaki & Takuma Oshiro & Jun Miki & Hiroki Yamada & Tatsuya Shimomura & Takahiro Kimura & Nozomu Furuta & Seiichi Saito & Shin Egawa, 2021. "Initial dose reduction of enzalutamide does not decrease the incidence of adverse events in castration-resistant prostate cancer," PLOS ONE, Public Library of Science, vol. 16(10), pages 1-10, October.
    2. Martina Troiani & Manuel Colucci & Mariantonietta D’Ambrosio & Ilaria Guccini & Emiliano Pasquini & Angelica Varesi & Aurora Valdata & Simone Mosole & Ajinkya Revandkar & Giuseppe Attanasio & Andrea R, 2022. "Single-cell transcriptomics identifies Mcl-1 as a target for senolytic therapy in cancer," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    3. Nader Al-Nakouzi & Chris Kedong Wang & Htoo Zarni Oo & Irina Nelepcu & Nada Lallous & Charlotte B. Spliid & Nastaran Khazamipour & Joey Lo & Sarah Truong & Colin Collins & Desmond Hui & Shaghayegh Esf, 2022. "Reformation of the chondroitin sulfate glycocalyx enables progression of AR-independent prostate cancer," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    4. Marco Bolis & Daniela Bossi & Arianna Vallerga & Valentina Ceserani & Manuela Cavalli & Daniela Impellizzieri & Laura Di Rito & Eugenio Zoni & Simone Mosole & Angela Rita Elia & Andrea Rinaldi & Ricar, 2021. "Dynamic prostate cancer transcriptome analysis delineates the trajectory to disease progression," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    5. Ni Li & Qiuli Liu & Ying Han & Siyu Pei & Bisheng Cheng & Junyu Xu & Xiang Miao & Qiang Pan & Hanling Wang & Jiacheng Guo & Xuege Wang & Guoying Zhang & Yannan Lian & Wei Zhang & Yi Zang & Minjia Tan , 2022. "ARID1A loss induces polymorphonuclear myeloid-derived suppressor cell chemotaxis and promotes prostate cancer progression," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    6. Bhavana Palakurthi & Shaneann R. Fross & Ian H. Guldner & Emilija Aleksandrovic & Xiyu Liu & Anna K. Martino & Qingfei Wang & Ryan A. Neff & Samantha M. Golomb & Cheryl Lewis & Yan Peng & Erin N. Howe, 2023. "Targeting CXCL16 and STAT1 augments immune checkpoint blockade therapy in triple-negative breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    7. Lauriane Galle-Treger & Doumet Georges Helou & Christine Quach & Emily Howard & Benjamin P. Hurrell & German R. Aleman Muench & Pedram Shafiei-Jahani & Jacob D. Painter & Andrea Iorga & Lily Dara & Ju, 2022. "Autophagy impairment in liver CD11c+ cells promotes non-alcoholic fatty liver disease through production of IL-23," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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