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Clinical Impact of the Increase in Immunosuppressive Cell-Related Gene Expression in Urine Sediment during Intravesical Bacillus Calmette-Guerin.


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

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Publications

Clinical Impact of the Increase in Immunosuppressive Cell-Related Gene Expression in Urine Sediment during Intravesical Bacillus Calmette-Guérin.

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]

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