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. (3rd August 2019)

• Record Type: Journal Article
• Authors: Martínez, Roberto; Tapia, Gustavo; De Muga, Silvia; Hernández, Alba; Cao, Maria González; Teixidó, Cristina; Urrea, Victor; García, Elisabet; Pedreño-López, Sònia; Ibarz, Luis; Blanco, Julià; Clotet, Bonaventura; Cabrera, Cecilia
• Is Part Of: Oncoimmunology. Volume 8:Number 8(2019)
• Publication Date: 2019-08-03
• Subjects: NMIBC -- BCG immunotherapy -- GATA-3 -- T-bet -- NLR -- biomarker; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2019.1602460
• Languages: English
• ISSNs: 2162-402X

Abstract

ABSTRACT: 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.