OP0023 CTLA4 single nucleotide polymorphisms correlate with response to BCG immunotherapy

Abstract

Background Although BCG is the gold standard for non-muscle invasive bladder cancer, there is a significant non-responder rate. The reasons for this are not known, although single nucleotide polymorphisms (SNPs) in some genes correlate with response to therapy. Bladder cancer patients who were treated with anti-CTLA4 antibodies had increased CD4 + ICOS hi IFN γ expressing T cells over Treg cell numbers in the bladder and peripheral blood. Therefore seven SNPs in the CTLA4 gene (rs733618, rs4553808, rs5742909, rs231775, rs3087243, rs7565213, rs960792) that regulate protein expression and function were chosen for analysis. Methods Institutional review board approval was obtained for this project. SNPs in 138 bladder cancer patients, who had previously been treated with BCG and for whom long-term follow-up data were available, and 146 healthy controls were analysed. Genomic DNA was extracted and subjected to PCR followed by high resolution melt (HRM) analysis and sequence analyses. Findings There were no differences in the incidence of SNPs between healthy controls and patients. By Kaplan–Meier analysis, GA at rs4553808 (148 months) and CT at rs5742909 (167 months) correlated with longer time to recurrence. By Cox regression analysis, CT at rs5742909; AA at rs3087243; AA and AG at rs7565213 and TT at rs960792 were significantly correlated with reduced risk of recurrence ( p p p p Interpretation rs231775 GG is associated with significantly increased T-cell activation. Here, rs231775 GA was associated with increased risk of disease progression, but not AA, which is expressed at a lower level in our population. These results indicate that CTLA4 blockade could be a beneficial co-therapy for some bladder cancer patients.