Anti-PD-1 antibody decreases tumour-infiltrating regulatory T cells
Anti-PD-1 antibody decreases tumour-infiltrating regulatory T cells
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DOI：
10.1186/s12885-019-6499-y
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发表时间：
2020-01-08
期刊：
影响因子：
3.8
通讯作者：
Saito, Naoto
中科院分区：
文献类型：
--
作者：
Yoshida, Kazushige;Okamoto, Masanori;Saito, Naoto
癌症的治疗方法有很多种。近年来，免疫疗法，特别是免疫检查点抑制剂，是研究的重点。免疫检查点抑制剂种类繁多，但其作用差异及机制尚不清楚。一些报道表明，抗pd -1抗体的应答率优于抗pd - l1抗体，并可能产生不同的作用机制。另一方面，Treg也表达PD-1；然而，他们的关系仍不清楚。方法采用体外培养骨肉瘤细胞系和小鼠骨肉瘤模型。在体外，我们用流式细胞术分析了IFN γ对细胞株表面PD-L1表达的影响。在体内，将小鼠骨肉瘤细胞系LM8皮下移植到小鼠背部。腹腔注射小鼠抗pd -1抗体。用流式细胞术分析抗pd -1抗体对肿瘤存活及T细胞比例的影响。结果发现IFN γ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抗体的施用抑制了肿瘤体积的增加并延长了总生存时间。在肿瘤微环境中，我们发现抗pd -1抗体的施用降低了肿瘤内的Treg，增加了肿瘤浸润淋巴细胞。本研究首次阐明了pd -1抗体降低Treg的抗肿瘤作用机制，并预期这一发现将为癌症治疗带来新方法的发展。
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 IFN gamma 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 IFN gamma 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.