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ABSTRACT: Background
The aim of this study is to evaluate the clinical impact of intravesical Bacillus Calmette-Guérin (BCG)-induced changes in blood/urinary immune markers.Methods
Time-course changes in blood/urinary clinical parameters and mRNA expression of 13 genes in urine sediment taken eight times during the treatment course of intravesical BCG (before, every 2 weeks for 8 weeks, and after) in 24 patients with non-muscle invasive bladder cancer. The genes examined include cellular markers of four immune checkpoint proteins (PD-L1, PD-L2, PD-1, and CTLA-4), immunosuppressive cells (regulatory T cells, tumor-associated macrophages, and myeloid-derived suppressor cells), pan-T lymphocytes, B lymphocytes, and neutrophils.Results
Significant transient increase in gene expression was observed for PD-L1, PD-1, FOXP3, and CD204 at 6-8 doses of BCG. The patients were stratified into two groups depending on the number of genes with increased mRNA expression. Fourteen (58%) had 0-1 genes upregulated, while 10 (42%) had 2-4 genes with increased expression. No patient in the 0-1 group experienced recurrence, while 70% of patients in the 2-4 group experienced recurrence (p value = 0.037, hazard ratio = 5.93).Conclusions
Our findings suggested that increases in more than one of PD-L1, PD-1, FOXP3, and CD204, expression in the urine sediments was associated with resistance to BCG treatment.
SUBMITTER: Miyake M
PROVIDER: S-EPMC6630414 | biostudies-literature | 2019 Jun
REPOSITORIES: biostudies-literature
Miyake Makito M Hori Shunta S Ohnishi Sayuri S Owari Takuya T Iida Kota K Ohnishi Kenta K Morizawa Yosuke Y Gotoh Daisuke D Itami Yoshitaka Y Nakai Yasushi Y Inoue Takeshi T Anai Satoshi S Torimoto Kazumasa K Aoki Katsuya K Fujii Tomomi T Tanaka Nobumichi N Fujimoto Kiyohide K
Diseases (Basel, Switzerland) 20190618 2
<h4>Background</h4>The aim of this study is to evaluate the clinical impact of intravesical Bacillus Calmette-Guérin (BCG)-induced changes in blood/urinary immune markers.<h4>Methods</h4>Time-course changes in blood/urinary clinical parameters and mRNA expression of 13 genes in urine sediment taken eight times during the treatment course of intravesical BCG (before, every 2 weeks for 8 weeks, and after) in 24 patients with non-muscle invasive bladder cancer. The genes examined include cellular m ...[more]