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】
Free