BACKGROUND There are many types of therapies for cancer. In these days, immunotherapies, especially immune checkpoint inhibitors, are focused on. Though many types of immune checkpoint inhibitors are there, the difference of effect and its mechanism are unclear. Some reports suggest the response rate of anti-PD-1 antibody is superior to that of anti-PD-L1 antibody and could potentially produce different mechanisms of action. On the other hand, Treg also express PD-1; however, their relationship remains unclear. METHODS In this study, we used osteosarcoma cell lines in vitro and osteosarcoma mouse model in vivo. In vitro, we analyzed the effect of IFNγ for expression of PD-L1 on the surface of cell lines by flowcytometry. In vivo, murine osteosarcoma cell line LM8 was subcutaneously transplanted into the dorsum of mice. Mouse anti-PD-1 antibody was intraperitoneally administered. we analysed the effect for survival of anti-PD-1 antibody and proportion of T cells in the tumour by flowcytometry. RESULTS We discovered that IFNγ increased PD-L1 expression on the surface of osteosarcoma cell lines. In assessing the relationship between anti-PD-1 antibody and Treg, we discovered the administration of anti-PD-1 antibody suppresses increases in tumour volume and prolongs overall survival time. In the tumour microenvironment, we found that the administration of anti-PD-1 antibody decreased Treg within the tumour and increased tumour-infiltrating lymphocytes. CONCLUSIONS Here we clarify for the first time an additional mechanism of anti-tumour effect-as exerted by anti-PD-1 antibody decreasing Treg- we anticipate that our findings will lead to the development of new methods for cancer treatment.

中文翻译：

---

抗PD-1抗体可减少肿瘤浸润的调节性T细胞。

背景技术存在许多类型的癌症疗法。这些天来，免疫疗法，尤其是免疫检查点抑制剂被关注。尽管存在多种类型的免疫检查点抑制剂，但其作用差异及其作用机制尚不清楚。一些报道表明抗PD-1抗体的应答率优于抗PD-L1抗体的应答率，并且可能潜在地产生不同的作用机制。另一方面，Treg也表达PD-1。但是，他们之间的关系仍然不清楚。方法在本研究中，我们在体外使用了骨肉瘤细胞系，在体内使用了骨肉瘤小鼠模型。在体外，我们通过流式细胞术分析了IFNγ对PD-L1在细胞系表面表达的影响。在体内，将鼠骨肉瘤细胞系LM8皮下移植到小鼠的背部。腹膜内施用小鼠抗PD-1抗体。我们通过流式细胞术分析了抗PD-1抗体的存活率和肿瘤中T细胞的比例。结果我们发现IFNγ增加了骨肉瘤细胞系表面PD-L1的表达。在评估抗PD-1抗体与Treg之间的关系时，我们发现抗PD-1抗体的给药可抑制肿瘤体积的增加并延长总体生存时间。在肿瘤微环境中，我们发现抗PD-1抗体的使用降低了肿瘤内的Treg，并增加了肿瘤浸润淋巴细胞。