Portal de Periódicos da CAPES

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

2019; Landes Bioscience; Volume: 8; Issue: 8 Linguagem: Inglês

10.1080/2162402x.2019.1602460

2162-402X

Roberto Martínez, Gustavo Tapia, Silvia de Muga, Alba Hernández, María González Cao, Cristina Teixidó, Víctor Urrea, Elisabet García, Sònia Pedreño‐López, L. Ibarz, Julià Blanco, Bonaventura Clotet, Cecilia Cabrera,

Inflammatory Biomarkers in Disease Prognosis

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.