Abstract
The aim of this study was to monitor changes in the expression of immune-related genes in the bladder after tumor implantation. Mice were orthotopically implanted with MB49-PSA cells (C57BL/6 mice) on day 1 and terminated on days 7, 14, 21, and 28. Another mouse model (MBT-2/C3H mice) was examined at day 7. Gene expression analysis was performed using a TaqMan Low Density Mouse Immune Panel (Applied Biosystems, USA) on RNA extracted from the bladders. Selected genes were reconfirmed by real-time PCR analysis and RT-PCR on the mRNA from other animals. Immune suppressive (IL13, IL1β, PTGS2, NOS2, IL10, CTLA4, and CCL22) and immune stimulatory genes (CSF2, GZMB, IFNγ, CXCL10, TNFα, CD80, IL12a, and IL6) and AGTR2 were increased by day 7. By day 28, IL10, CCL2, CCL5, CXCL11, CTLA4, GZMB, IFNγ, CSF2, and IL6 were significantly increased. Therapeutic strategies involving TH1 induction and TH2 dampening may improve responses to immunotherapy.
Highlights
Bladder cancer is the 7th most common cancer worldwide
Transurethral resection of the bladder tumor (TURBT) followed by Mycobacterium bovis, Bacillus Calmette Guerin (BCG) immunotherapy reduces the incidence of recurrence, but some 30–50% of patients do not respond to therapy [1, 2]
Recurrences are attributed to remnant tumor cells missed during surgery as a second surgical procedure prior to BCG therapy improves the response to therapy [1]
Summary
Though bladder cancer is not usually life threatening, it is prone to recurrences which may progress to invasive cancer. Transurethral resection of the bladder tumor (TURBT) followed by Mycobacterium bovis, Bacillus Calmette Guerin (BCG) immunotherapy reduces the incidence of recurrence, but some 30–50% of patients do not respond to therapy [1, 2]. Recurrences are attributed to remnant tumor cells missed during surgery as a second surgical procedure prior to BCG therapy improves the response to therapy [1]. The immune response induced by BCG immunotherapy may inadvertently ensure the survival of less immunogenic remnant tumor cells which could give rise to recurrence and progression. The increased incidence of progression in patients who fail BCG immunotherapy gives some credence to this latter possibility [1]
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