dc.contributor.author | Calcinotto, A | |
dc.contributor.author | Spataro, C | |
dc.contributor.author | Zagato, E | |
dc.contributor.author | Di Mitri, D | |
dc.contributor.author | Gil, V | |
dc.contributor.author | Crespo, M | |
dc.contributor.author | De Bernardis, G | |
dc.contributor.author | Losa, M | |
dc.contributor.author | Mirenda, M | |
dc.contributor.author | Pasquini, E | |
dc.contributor.author | Rinaldi, A | |
dc.contributor.author | Sumanasuriya, S | |
dc.contributor.author | Lambros, MB | |
dc.contributor.author | Neeb, A | |
dc.contributor.author | Lucianò, R | |
dc.contributor.author | Bravi, CA | |
dc.contributor.author | Nava-Rodrigues, D | |
dc.contributor.author | Dolling, D | |
dc.contributor.author | Prayer-Galetti, T | |
dc.contributor.author | Ferreira, A | |
dc.contributor.author | Briganti, A | |
dc.contributor.author | Esposito, A | |
dc.contributor.author | Barry, S | |
dc.contributor.author | Yuan, W | |
dc.contributor.author | Sharp, A | |
dc.contributor.author | de Bono, J | |
dc.contributor.author | Alimonti, A | |
dc.date.accessioned | 2019-05-03T15:19:50Z | |
dc.date.issued | 2018-07-19 | |
dc.identifier.citation | Nature, 2018, 559 (7714), pp. 363 - 369 | |
dc.identifier.issn | 0028-0836 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3218 | |
dc.identifier.eissn | 1476-4687 | |
dc.identifier.doi | 10.1038/s41586-018-0266-0 | |
dc.description.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. | |
dc.format | Print-Electronic | |
dc.format.extent | 363 - 369 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PORTFOLIO | |
dc.rights.uri | https://www.rioxx.net/licenses/all-rights-reserved | |
dc.subject | Animals | |
dc.subject | Humans | |
dc.subject | Mice | |
dc.subject | Phenylthiohydantoin | |
dc.subject | Receptors, Interleukin | |
dc.subject | Receptors, Androgen | |
dc.subject | Androgens | |
dc.subject | Signal Transduction | |
dc.subject | Cell Proliferation | |
dc.subject | Cell Survival | |
dc.subject | Male | |
dc.subject | Interleukin-23 | |
dc.subject | Nuclear Receptor Subfamily 1, Group F, Member 3 | |
dc.subject | Androgen Receptor Antagonists | |
dc.subject | Prostatic Neoplasms, Castration-Resistant | |
dc.subject | Myeloid-Derived Suppressor Cells | |
dc.title | IL-23 secreted by myeloid cells drives castration-resistant prostate cancer. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2018-05-29 | |
rioxxterms.versionofrecord | 10.1038/s41586-018-0266-0 | |
rioxxterms.licenseref.uri | https://www.rioxx.net/licenses/all-rights-reserved | |
rioxxterms.licenseref.startdate | 2018-07 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Nature | |
pubs.issue | 7714 | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Cancer Biomarkers | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Cancer Biomarkers | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Translational Therapeutics | |
pubs.organisational-group | /ICR/Students | |
pubs.organisational-group | /ICR/Students/PhD and MPhil | |
pubs.organisational-group | /ICR/Students/PhD and MPhil/16/17 Starting Cohort | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Cancer Biomarkers | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Cancer Biomarkers | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Translational Therapeutics | |
pubs.organisational-group | /ICR/Students | |
pubs.organisational-group | /ICR/Students/PhD and MPhil | |
pubs.organisational-group | /ICR/Students/PhD and MPhil/16/17 Starting Cohort | |
pubs.publication-status | Published | |
pubs.volume | 559 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Cancer Biomarkers | |
icr.researchteam | Prostate Cancer Targeted Therapy Group | |
icr.researchteam | Translational Therapeutics | |
dc.contributor.icrauthor | Sumanasuriya, Semini | |
dc.contributor.icrauthor | Sharp, Adam | |
dc.contributor.icrauthor | De Bono, Johann | |