Purpose: Immune checkpoint inhibitors (ICIs) in general have shown poor efficacy in bladder cancer (BCa). The purpose of this project was to determine whether photodynamic therapy (PDT) with BCa-specific porphyrin-based PLZ4-nanoparticles (PNP) potentiated ICI. Experimental Design: SV40 T/Ras double-transgenic mice bearing spontaneous BCa and C57BL/6 mice carrying syngeneic bladder cancer models were used to determine the efficacy and conduct molecular correlative studies. Results: PDT with PNP generated reactive oxygen species, induced protein carbonylation and dendritic cell maturation. In SV40 T/Ras double-transgenic mice carrying spontaneous bladder cancer, the median survival was 33.7 days in the control, compared to 44.8 (p=0.0123), 52.6 (p=0.0054) and over 75 (p=0.0001) days in the anti-programmed cell death-1 antibody(anti-PD-1), PNP PDT and combination groups, respectively. At Day 75 when all mice in other groups died, only one in 7 mice in the combination group died. For the direct anti-tumor activity, compared to the control, the ani-PD-1, PNP PDT and combination groups induced a 40.25% (p=0.0003), 80.72% (p<0.0001) and 93.03% (p<0.0001) tumor reduction, respectively. For the abscopal anti-cancer immunity, the anti-PD-1, PNP PDT and combination groups induced tumor reduction of 45.73% (p=0.0001), 54.92% (p<0.0001) and 75.96% (p<0.0001), respectively. The combination treatment also diminished spontaneous and induced lung metastasis. Potential of immunotherapy by PNP PDT is multifactorial. Conclusions: In addition to its potential for photodynamic diagnosis and therapy, PNP PDT can synergize immunotherapy in treating locally advanced and metastatic bladder cancer. Clinical trials are warranted to determine the efficacy and toxicity of this combination.

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Objective: Increased pneumoperitoneum pressure during laparoscopic surgery can result in acute kidney injury. We aimed to clarify whether intraabdominal pressure tolerance is modified in various degrees of unilateral kidney hydronephrosis in rabbits. Methods: A total 90 rabbits were randomly allocated to three groups (group PN, PM and PS, i.e. rabbits with no, mild and severe hydronephrosis, respectively, subjected to intraabdominal pressures). Rabbits in group PM (n = 30) and group PS (n = 30) underwent a surgical procedure inducing a mild or severe left hydronephrosis. Rabbits in all groups were then allocated to 5 subgroups. Then, they were subjected to intraabdominal pressures of 0, 6, 9, 12, and 15 mm Hg, respectively. Acute kidney injury was assessed by measuring serum creatinine (Scr), blood urea nitrogen (BUN), tubular cell apoptosis, kidney injury molecule-1 (KIM-1) and cysteine-rich 61 (Cyr-61/CCN1) expression. Results: Acute kidney injury with increased tubular apoptosis and KIM-1 and Cyr-61 expression occurred when intraabdominal pressure reached 15, 15 and 9 mm Hg in PN, PM and PS groups, respectively. The Scr and BUN levels were similar in all groups. Conclusions: In rabbits, kidneys with severe hydronephrosis were more likely to suffer acute injury when they were exposed to pneumoperitoneal pressure.