The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland; and.
H. Lee Moffitt Cancer Center, University of South Florida, Tampa, Florida.
Cancer Immunol Res. 2014 Aug;2(8):725-31. doi: 10.1158/2326-6066.CIR-13-0213. Epub 2014 Mar 28.
Myeloid-derived suppressor cells (MDSC) play a significant role in tumor-induced immune suppression. Targeting their function could improve antitumor therapies. Previously, we demonstrated that phosphodiesterase 5 (PDE5) inhibition in MDSCs augmented antitumor immunity in murine models. Here, we show how the addition of the PDE5 inhibitor, tadalafil, in a patient with end-stage relapsed/refractory multiple myeloma reduced MDSC function and generated a dramatic and durable antimyeloma immune and clinical response. Strategies targeting MDSC function with PDE5 inhibitors represent a novel approach that can augment the efficacy of tumor-directed therapies.
髓系来源的抑制细胞（MDSC）在肿瘤诱导的免疫抑制中发挥重要作用。针对其功能可能会改善抗肿瘤治疗。此前，我们证明了在 MDSC 中抑制磷酸二酯酶 5（PDE5）可增强小鼠模型中的抗肿瘤免疫。在这里，我们展示了在一位终末期复发/难治性多发性骨髓瘤患者中添加 PDE5 抑制剂他达拉非如何降低 MDSC 的功能并产生显著和持久的抗骨髓瘤免疫和临床反应。使用 PDE5 抑制剂靶向 MDSC 功能的策略代表了一种可以增强肿瘤靶向治疗效果的新方法。
