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Research article

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

Kazushige Yoshida, Masanori Okamoto, Jun Sasaki, Chika Kuroda, Haruka Ishida, Katsuya Ueda, Hirokazu Ideta, Takayuki Kamanaka, Atsushi Sobajima, Takashi Takizawa, Manabu Tanaka, Kaoru Aoki, Takeshi Uemura, Hiroyuki Kato, Hisao Haniu, Naoto Saito

Abstract

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 tumor 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 tumor 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. keywords: PD-1, Treg, osteosarcoma, anti-PD-1 antibody.

Keywords
PD-1, Treg, osteosarcoma, anti-PD-1 antibody

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Preprint: Please note that this article has not completed peer review.
Research article

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

Kazushige Yoshida, Masanori Okamoto, Jun Sasaki, Chika Kuroda, Haruka Ishida, Katsuya Ueda, Hirokazu Ideta, Takayuki Kamanaka, Atsushi Sobajima, Takashi Takizawa, Manabu Tanaka, Kaoru Aoki, Takeshi Uemura, Hiroyuki Kato, Hisao Haniu, Naoto Saito

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Abstract

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 tumor 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 tumor 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. keywords: PD-1, Treg, osteosarcoma, anti-PD-1 antibody.

Figures

Background

Methods

Results

Discussion

Conclusions

Declarations

References

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