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Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
Distinct Gene Expression Patterns Identify Patients who Relapse After Neoadjuvant Pembrolizumab and Radical
Moritz J Reike1, Daniele Raggi2, Chiara Mercinelli2
1Department of Urologic Sciences, University of British Columbia, Vancouver, Canada; Department of Urology, Marien Hospital Herne, Ruhr-University Bochum, Germany.
Purpose:
The PURE-01 clinical trial reported the use of neoadjuvant treatment with pembrolizumab prior to radical cystectomy (RC) in patients with muscle-invasive bladder. Specific molecular subtypes and immune signatures were reported to be associated with a favorable survival. However, reports on the detailed tumor biology of patients relapsing after neoadjuvant pembrolizumab are lacking.
Materials And Methods:
Microarray data from transurethral resection of the bladder tumor (TURBT; n = 102) and matched RC (N = 25) tissue from patients in PURE-01 who experience a disease relapse were analyzed, with gene expression signatures and molecular subtypes. The Kaplan-Meier method was used to estimate differences in patient outcomes. Immune-signatures were split by median for survival analysis. All significance testing used a two-sided t-test at a threshold of P < .05.
Results:
The study cohort consisted of 102 patients, of whom N = 19 (19%) experienced relapse. Molecular subtyping revealed that neuroendocrine-like tumors had the worst outcomes, while tumors classified as Claudin-low did show only one recurrence event. Differential gene expression analysis identified genes associated with relapse, including KRT20, H19, and immune-associated genes such as CXCL9 and CXCL11.
Conclusion:
This study provides a detailed characterization of patients who relapsed after neoadjuvant pembrolizumab and RC and identifies distinct gene expression patterns associated with relapse. These findings may have implications for predicting patient response and guiding treatment decisions in the neoadjuvant setting.
