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

Article

关键词: SUPPRESSOR-CELLS;    ENZALUTAMIDE MDV3100;    ABIRATERONE ACETATE;    TUMOR PROGRESSION;    CLINICAL ACTIVITY;    DOCETAXEL;    MECHANISMS;    EXPRESSION;    SENESCENCE;    REGULATORS;   

DOI  :  10.1038/s41586-018-0266-0

来源: SCIE

【 摘 要 】

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.

【 授权许可】

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