Anti-PD-1 antibody decreases tumour-infiltrating regulatory T cells

被引:84
|
作者
Yoshida, Kazushige [1 ]
Okamoto, Masanori [1 ]
Sasaki, Jun [1 ]
Kuroda, Chika [2 ]
Ishida, Haruka [2 ]
Ueda, Katsuya [2 ]
Ideta, Hirokazu [1 ]
Kamanaka, Takayuki [1 ]
Sobajima, Atsushi [1 ]
Takizawa, Takashi [1 ]
Tanaka, Manabu [3 ]
Aoki, Kaoru [4 ]
Uemura, Takeshi [2 ]
Kato, Hiroyuki [1 ]
Haniu, Hisao [2 ]
Saito, Naoto [2 ]
机构
[1] Shinshu Univ, Dept Orthopaed Surg, Sch Med, Matsumoto, Nagano, Japan
[2] Shinshu Univ, Inst Biomed Sci, Interdisciplinary Cluster Cutting Edge Res, Asahi 3-1-1, Matsumoto, Nagano 3908621, Japan
[3] Okaya City Hosp, Dept Orthoped Surg, Okaya, Japan
[4] Shinshu Univ, Sch Hlth Sci, Phys Therapy Div, Sch Med, Matsumoto, Nagano, Japan
关键词
PD-1; Treg; Osteosarcoma; Anti-PD-1; antibody; IFN-GAMMA; CANCER; PD-L1; BLOCKADE; EXPRESSION; SUPPRESSION; EFFICACY; THERAPY; ROLES; FOXP3;
D O I
10.1186/s12885-019-6499-y
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
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页数:10
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