| Summary: | Yiqun Shao,1 Wenjing Zhu,2 Jun Da,1 Mingxi Xu,1 Yiwei Wang,1 Juan Zhou,1 Zhong Wang1 1Department of Urology, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Urology, Yueyang Hospital of integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China Abstract: Curcumin was recently discovered to strengthen immune response through multiple mechanisms. Cytotoxic CD8+ T-cells play a critical role in modulating anticancer immune response, but is severely restricted by T-cell exhaustion. Bladder carcinomas express PD-L1 and can abrogate CD8+ T-cell response. Thus, we hypothesized that bisdemethoxycurcumin, a natural dimethoxy derivative of curcumin, may provide a favorable environment for T-cell response against bladder cancer when used in combination with α-PD-L1 antibody. Immunocompetent C56BL/6 mouse models bearing subcutaneous or lung metastasized MB79 bladder cancer were established to validate this conjecture. We found that bisdemethoxycurcumin significantly increased intratumoral CD8+ T-cell infiltration, elevated the level of IFN-γ in the blood, and decreased the number of intratumoral myeloid-derived suppressor cells. Furthermore, α-PD-L1 antibody protected these amplified CD8+ T-cells from exhaustion, and therefore facilitated the secretion of IFN-γ, granzyme B, and perforin through these CD8+ T-cells. As a result, this combination treatment strategy significantly prolonged survival of intraperitoneal metastasized bladder cancer bearing mice, suggesting that bisdemethoxycurcumin in combination with α-PD-L1 antibody may be promising for bladder cancer patients. Keywords: bladder cancer, immunotherapy, bisdemethoxycurcumin, PD-L1, combination therapy, metastasis
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