Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, #88 Jiefang Road, Hangzhou, 310009, Zhejiang, PR China; Orthopedics Research Institute of Zhejiang University, No. 88, Jiefang Road, Hangzhou 310009, PR China.
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, PR China.
Biomaterials. 2019 Feb;192:128-139. doi: 10.1016/j.biomaterials.2018.11.019. Epub 2018 Nov 13.
Elevated expression of programmed death ligand-1 (PD-L1) on the surface of tumor cells can exhaust cytotoxic T lymphocyte cells and lead to the failure of anti-tumor immunity during the course of tumor treatment. Here, we implemented a combined regimen of tumor resection and bovine serum albumin-Zinc phthalocyanine-induced photodynamic therapy (PDT). To overcome the long-distance metastasis of osteosarcoma, we also explored the effects of PD-L1 down-regulation with PDT and the autophagy inhibitor 3-MA on osteosarcoma treatment. A dramatic anti-tumor effect induced by PDT was observed in a partial resection model, which revealed the potential clinical application of PDT during tumor resection. Meanwhile, we also confirmed the down-regulation of PD-L1 in osteosarcoma in response to PDT and 3-MA treatment, which significantly inhibited tumor growth in a model of tumor metastasis. The immunological response induced by the combination of the autophagy inhibitor and PDT suppressed osteosarcoma in vitro and in vivo, which indicated the potential application of this regimen for preventing tumor metastasis. The combination of PDT with multiple therapies has a potentially bright future as an osteosarcoma treatment strategy.
肿瘤细胞表面程序性死亡配体 1（PD-L1）的表达升高会使细胞毒性 T 淋巴细胞耗竭，导致肿瘤治疗过程中抗肿瘤免疫失败。在这里，我们实施了肿瘤切除联合牛血清白蛋白-锌酞菁诱导的光动力疗法（PDT）的联合方案。为了克服骨肉瘤的远距离转移，我们还探索了 PDT 联合自噬抑制剂 3-MA 下调 PD-L1 对骨肉瘤治疗的影响。在部分切除模型中观察到 PDT 引起的抗肿瘤作用明显，这揭示了 PDT 在肿瘤切除过程中的潜在临床应用。同时，我们还证实了 PDT 和 3-MA 治疗可下调骨肉瘤中的 PD-L1，这显著抑制了转移模型中的肿瘤生长。自噬抑制剂和 PDT 的联合诱导的免疫反应抑制了骨肉瘤的体内外生长，表明该方案在预防肿瘤转移方面具有潜在的应用前景。PDT 与多种疗法的联合具有作为骨肉瘤治疗策略的广阔前景。
