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.
Oncoimmunology. 2019 Apr 13*** epublish ***
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
Urology Department, Hospital Universitario Germans Trias i Pujol, IGTP, UAB, Badalona, Spain., Pathology Department, Hospital Universitario Germans Trias i Pujol, IGTP, UAB, Badalona, Spain., IrsiCaixa AIDS Research Institute, Germans Trias i Pujol Research Institute (IGTP) UAB, Badalona, Spain., Dr. Rosell Oncology Institute, Quirón Dexeus University Hospital, Barcelona, Spain., Pangaea Biotech, Quirón Dexeus University Hospital, Barcelona, Spain.