IL-23 secreted by myeloid cells drives castration-resistant prostate cancer.
Nature
; 559(7714): 363-369, 2018 07.
Article
en En
| MEDLINE
| ID: mdl-29950727
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Interleucina-23
/
Neoplasias de la Próstata Resistentes a la Castración
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Células Supresoras de Origen Mieloide
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Nature
Año:
2018
Tipo del documento:
Article
País de afiliación:
Suiza