dc.contributor.author | Fenor de la Maza, MD | |
dc.contributor.author | Chandran, K | |
dc.contributor.author | Rekowski, J | |
dc.contributor.author | Shui, IM | |
dc.contributor.author | Gurel, B | |
dc.contributor.author | Cross, E | |
dc.contributor.author | Carreira, S | |
dc.contributor.author | Yuan, W | |
dc.contributor.author | Westaby, D | |
dc.contributor.author | Miranda, S | |
dc.contributor.author | Ferreira, A | |
dc.contributor.author | Seed, G | |
dc.contributor.author | Crespo, M | |
dc.contributor.author | Figueiredo, I | |
dc.contributor.author | Bertan, C | |
dc.contributor.author | Gil, V | |
dc.contributor.author | Riisnaes, R | |
dc.contributor.author | Sharp, A | |
dc.contributor.author | Rodrigues, DN | |
dc.contributor.author | Rescigno, P | |
dc.contributor.author | Tunariu, N | |
dc.contributor.author | Liu, XQ | |
dc.contributor.author | Cristescu, R | |
dc.contributor.author | Schloss, C | |
dc.contributor.author | Yap, C | |
dc.contributor.author | de Bono, JS | |
dc.coverage.spatial | Netherlands | |
dc.date.accessioned | 2022-06-30T11:23:46Z | |
dc.date.available | 2022-06-30T11:23:46Z | |
dc.date.issued | 2022-04-28 | |
dc.identifier | S2588-9311(22)00060-8 | |
dc.identifier.citation | European Urology Oncology, 2022, pp. S2588-9311(22)00060-8 - | |
dc.identifier.issn | 2588-9311 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5199 | |
dc.identifier.eissn | 2588-9311 | |
dc.identifier.eissn | 2588-9311 | |
dc.description.abstract | BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease in which molecular stratification is needed to improve clinical outcomes. The identification of predictive biomarkers can have a major impact on the care of these patients, but the availability of metastatic tissue samples for research in this setting is limited. OBJECTIVE: To study the prevalence of immune biomarkers of potential clinical utility to immunotherapy in mCRPC and to determine their association with overall survival (OS). DESIGN, SETTING, AND PARTICIPANTS: From 100 patients, mCRPC biopsies were assayed by whole exome sequencing, targeted next-generation sequencing, RNA sequencing, tumor mutational burden, T-cell-inflamed gene expression profile (TcellinfGEP) score (Nanostring), and immunohistochemistry for programmed cell death 1 ligand 1 (PD-L1), ataxia-telangiectasia mutated (ATM), phosphatase and tensin homolog (PTEN), SRY homology box 2 (SOX2), and the presence of neuroendocrine features. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The phi coefficient determined correlations between biomarkers of interest. OS was assessed using Kaplan-Meier curves and adjusted hazard ratios (aHRs) from Cox regression. RESULTS AND LIMITATIONS: PD-L1 and SOX2 protein expression was detected by immunohistochemistry (combined positive score ≥1 and >5% cells, respectively) in 24 (33%) and 27 (27%) mCRPC biopsies, respectively; 23 (26%) mCRPC biopsies had high TcellinfGEP scores (>-0.318). PD-L1 protein expression and TcellinfGEP scores were positively correlated (phi 0.63 [0.45; 0.76]). PD-L1 protein expression (aHR: 1.90 [1.05; 3.45]), high TcellinfGEP score (aHR: 1.86 [1.04; 3.31]), and SOX2 expression (aHR: 2.09 [1.20; 3.64]) were associated with worse OS. CONCLUSIONS: PD-L1, TcellinfGEP score, and SOX2 are prognostic of outcome from the mCRPC setting. If validated, predictive biomarker studies incorporating survival endpoints need to take these findings into consideration. PATIENT SUMMARY: This study presents an analysis of immune biomarkers in biopsies from patients with metastatic prostate cancer. We describe tumor alterations that predict prognosis that can impact future studies. | |
dc.format | Print-Electronic | |
dc.format.extent | S2588-9311(22)00060-8 - | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | ELSEVIER | |
dc.relation.ispartof | European Urology Oncology | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | Correlation | |
dc.subject | Overall survival | |
dc.subject | PD-L1 | |
dc.subject | SOX2 | |
dc.subject | T-cell–inflamed gene expression profile | |
dc.title | Immune Biomarkers in Metastatic Castration-resistant Prostate Cancer. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2022-04-13 | |
dc.date.updated | 2022-06-30T11:22:15Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1016/j.euo.2022.04.004 | |
rioxxterms.licenseref.startdate | 2022-04-28 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/35491356 | |
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/Clinical Trials & Statistics Unit | |
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/18/19 Starting Cohort | |
pubs.organisational-group | /ICR/Students/PhD and MPhil/20/21 Starting Cohort | |
pubs.publication-status | Published online | |
icr.researchteam | Cancer Biomarkers | |
icr.researchteam | Translational Therapeutic | |
icr.researchteam | Clin Trials & Stats Unit | |
icr.researchteam | PrCa Targeted Therapy | |
dc.contributor.icrauthor | Gurel, Bora | |
dc.contributor.icrauthor | Carreira, Suzanne | |
dc.contributor.icrauthor | Westaby, Daniel | |
dc.contributor.icrauthor | Miranda, Susana | |
dc.contributor.icrauthor | Sharp, Adam | |
dc.contributor.icrauthor | Rescigno, Pasquale | |
dc.contributor.icrauthor | Yap, Christina | |
dc.contributor.icrauthor | De Bono, Johann | |