Combined assessment of peritumoral Th1/Th2 polarization and peripheral immunity as a new biomarker in the prediction of BCG response in patients with high-risk NMIBC

Roberto Martínez, Gustavo Tapia, Silvia De Muga, Alba Hernández, Maria González Cao, Cristina Teixidó, Victor Urrea, Elisabet García, Sònia Pedreño-López, Luis Ibarz, Julià Blanco, Bonaventura Clotet, Cecilia Cabrera

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Abstract

© 2019, © 2019 Taylor & Francis Group, LLC. Intravesical Bacille Calmette-Guérin (BCG) remains the most effective treatment for high-risk non-muscle-invasive bladder cancer (NMIBC), unfortunately there is no validated biomarker to predict clinical outcome. Here we tried to explore the possibility that a combination of the density of peritumoral infiltrating cells (Th1, Th2 and PD-L1) and the composition of peripheral immune cells (neutrophil and lymphocyte counts) could generate a more reliable prognostic biomarker. Twenty-two patients with high-risk NMIBC treated with BCG (10 BCG nonresponders and 12 BCG responders) were selected. BCG responders had significantly lower level of peritumoral T-bet+ cells with an associated higher GATA-3+/T-bet+ ratio (p = 0.04, p = 0.02, respectively). Furthermore, the immune polarization in tissue (GATA-3+/T-bet+ ratio) adjusted for the systemic inflammation (neutrophil-to-lymphocyte ratio) showed a significantly higher association with the BCG response (p = 0.004). A survival analysis demonstrated prolonged recurrence-free survival (RFS) in patients with a lower T-bet+/Lymphocyte ratio and higher GTR/NLR (p = 0.01). No association was observed between peritumoral PD-L1+ expression and the BCG response. In conclusion, alterations in overall immune function, both local and systemic, may influence the therapeutic response to BCG, therefore a combined analysis of tumoral (Th2/Th1 ratio) and peripheral (NLR) immune composition prior to treatment may be a promising approach to predict the BCG response in high-risk NMIBC patients.
Original languageEnglish
Article numbere1602460
JournalOncoImmunology
Volume8
DOIs
Publication statusPublished - 1 Jan 2019

Keywords

  • BCG immunotherapy
  • biomarker
  • GATA-3
  • NLR
  • NMIBC
  • T-bet

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    Martínez, R., Tapia, G., De Muga, S., Hernández, A., Cao, M. G., Teixidó, C., Urrea, V., García, E., Pedreño-López, S., Ibarz, L., Blanco, J., Clotet, B., & Cabrera, C. (2019). Combined assessment of peritumoral Th1/Th2 polarization and peripheral immunity as a new biomarker in the prediction of BCG response in patients with high-risk NMIBC. OncoImmunology, 8, [e1602460]. https://doi.org/10.1080/2162402X.2019.1602460