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 de'rivative of curcumin, may provide a favorable environment for T-cell response against bladder cancer when used in combination with a-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 a-PD-L1 antibody may be promising for bladder cancer patients.
CITATION STYLE
Sshao, Y., Zhu, W., Da, J., Xu, M., Wang, Y., Zhou, J., & Wang, Z. (2017). Bisdemethoxycurcumin in combination with α-PD-L1 antibody boosts immune response against bladder cancer. OncoTargets and Therapy, 10, 2675–2683. https://doi.org/10.2147/OTT.S130653
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