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Immune Biomarkers in Metastatic Castration-resistant Prostate Cancer.
Fenor de la Maza, María Dolores; Chandran, Khobe; Rekowski, Jan; Shui, Irene M; Gurel, Bora; Cross, Emily; Carreira, Suzanne; Yuan, Wei; Westaby, Daniel; Miranda, Susana; Ferreira, Ana; Seed, George; Crespo, Mateus; Figueiredo, Ines; Bertan, Claudia; Gil, Veronica; Riisnaes, Ruth; Sharp, Adam; Rodrigues, Daniel Nava; Rescigno, Pasquale; Tunariu, Nina; Liu, Xiao Qiao; Cristescu, Razvan; Schloss, Charles; Yap, Christina; de Bono, Johann S.
Afiliación
  • Fenor de la Maza MD; The Institute of Cancer Research, London, UK; The Royal Marsden Hospital, London, UK.
  • Chandran K; The Institute of Cancer Research, London, UK; The Royal Marsden Hospital, London, UK.
  • Rekowski J; The Institute of Cancer Research, London, UK.
  • Shui IM; Merck & Co., Inc., Kenilworth, NJ, USA.
  • Gurel B; The Institute of Cancer Research, London, UK.
  • Cross E; The Institute of Cancer Research, London, UK.
  • Carreira S; The Institute of Cancer Research, London, UK.
  • Yuan W; The Institute of Cancer Research, London, UK.
  • Westaby D; The Institute of Cancer Research, London, UK; The Royal Marsden Hospital, London, UK.
  • Miranda S; The Institute of Cancer Research, London, UK; The Royal Marsden Hospital, London, UK.
  • Ferreira A; The Institute of Cancer Research, London, UK.
  • Seed G; The Institute of Cancer Research, London, UK.
  • Crespo M; The Institute of Cancer Research, London, UK.
  • Figueiredo I; The Institute of Cancer Research, London, UK.
  • Bertan C; The Institute of Cancer Research, London, UK.
  • Gil V; The Institute of Cancer Research, London, UK.
  • Riisnaes R; The Institute of Cancer Research, London, UK.
  • Sharp A; The Institute of Cancer Research, London, UK; The Royal Marsden Hospital, London, UK.
  • Rodrigues DN; Royal Free Hospital, London, UK.
  • Rescigno P; Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Turin, Italy.
  • Tunariu N; The Institute of Cancer Research, London, UK; The Royal Marsden Hospital, London, UK.
  • Liu XQ; Merck & Co., Inc., Kenilworth, NJ, USA.
  • Cristescu R; Merck & Co., Inc., Kenilworth, NJ, USA.
  • Schloss C; Merck & Co., Inc., Kenilworth, NJ, USA.
  • Yap C; The Institute of Cancer Research, London, UK.
  • de Bono JS; The Institute of Cancer Research, London, UK; The Royal Marsden Hospital, London, UK. Electronic address: johann.de-bono@icr.ac.uk.
Eur Urol Oncol ; 5(6): 659-667, 2022 12.
Article en En | MEDLINE | ID: mdl-35491356
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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Antígeno B7-H1 / Neoplasias de la Próstata Resistentes a la Castración Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans / Male Idioma: En Revista: Eur Urol Oncol Año: 2022 Tipo del documento: Article País de afiliación: Reino Unido
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Antígeno B7-H1 / Neoplasias de la Próstata Resistentes a la Castración Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans / Male Idioma: En Revista: Eur Urol Oncol Año: 2022 Tipo del documento: Article País de afiliación: Reino Unido