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

  • Calcinotto A Institute of Oncology Research (IOR), Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
  • Spataro C Institute of Oncology Research (IOR), Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
  • Zagato E Institute of Oncology Research (IOR), Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
  • Di Mitri D Institute of Oncology Research (IOR), Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
  • Gil V The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK.
  • Crespo M The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK.
  • De Bernardis G Institute of Oncology Research (IOR), Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
  • Losa M Institute of Oncology Research (IOR), Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
  • Mirenda M Institute of Oncology Research (IOR), Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
  • Pasquini E Institute of Oncology Research (IOR), Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
  • Rinaldi A Institute of Oncology Research (IOR), Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
  • Sumanasuriya S The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK.
  • Lambros MB The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK.
  • Neeb A The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK.
  • Lucianò R Division of Oncology, Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
  • Bravi CA Division of Oncology, Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
  • Nava-Rodrigues D The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK.
  • Dolling D The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK.
  • Prayer-Galetti T Department of Urology, University of Padova, Padova, Italy.
  • Ferreira A The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK.
  • Briganti A Division of Oncology, Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
  • Esposito A Experimental Imaging Center, San Raffaele Scientific Institute, Milan, Italy.
  • Barry S IMED Oncology AstraZeneca, Li Ka Shing Centre, Cambridge, UK.
  • Yuan W The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK.
  • Sharp A The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK.
  • de Bono J The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK.
  • Alimonti A Institute of Oncology Research (IOR), Oncology Institute of Southern Switzerland, Bellinzona, Switzerland. andrea.alimonti@ior.iosi.ch.
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  • 2018-06-29
Published in:
  • Nature. - 2018
Androgen Receptor Antagonists
Androgens
Animals
Cell Proliferation
Cell Survival
Humans
Interleukin-23
Male
Mice
Myeloid-Derived Suppressor Cells
Nuclear Receptor Subfamily 1, Group F, Member 3
Phenylthiohydantoin
Prostatic Neoplasms, Castration-Resistant
Receptors, Androgen
Receptors, Interleukin
Signal Transduction
English 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.
Language
  • English
Open access status
green
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Persistent URL
https://sonar.ch/global/documents/88014
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