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Human Vγ9Vδ2 T cells exert anti-tumor activity independently of PD-L1 expression in tumor cells

発表形態:
原著論文
主要業績:
主要業績
単著・共著:
共著
発表年月:
2021年10月
DOI:
10.1016/j.bbrc.2021.08.005
会議属性:
指定なし
査読:
有り
リンク情報:

日本語フィールド

著者:
*Mako Tomogane, Yusuke Sano, Daiki Shimizu, Teruki Shimizu, Masatsugu Miyashita, Yuki Toda, Shigekuni Hosogi, Yoshimasa Tanaka, Shinya Kimura, Eishi Ashihara
題名:
Human Vγ9Vδ2 T cells exert anti-tumor activity independently of PD-L1 expression in tumor cells
発表情報:
Biochem Biophys Res Commun 巻: 573 ページ: 132-139
キーワード:
PD-1; PD-L1; RNA interference; Vγ9Vδ2 T cell; γδ T cell
概要:
Human γδ T cells expressing Vγ9Vδ2 T cell receptors play a crucial role in the innate immune system and have an attracted interest as effector cells in adoptive cellular immunotherapy. However, the efficacy of adoptive cellular immunotherapy for the treatment of tumors requires overcoming the immunosuppressive microenvironment. αβ T cell inhibition in the tumor microenvironment is associated with programmed death-ligand 1 (PD-L1) expression level. Vγ9Vδ2 T cells (abbreviated as γδ T cells here) exert potent cytotoxic effects in various cancers; however, γδ T cell activity in relation to the level of PD-L1 expression in cancer cells remains unclear, and the association between the PD-1/PD-L1 axis and γδ T cell cytotoxicity needs to be investigated. In this study, PD-1 blockade did not increase the cytotoxicity of γδ T cells against PD-L1high cancer cells. However, the anti-PD-L1 monoclonal antibody (mAb) enhanced the cytotoxicity of γδ T cells against a subset of cancer cells, whereas PD-L1 knockdown did not increase the cytotoxicity of γδ T cells. We also found that the expression levels of PD-L1 were positively correlated with the changes of γδ T cells cytotoxicity induced by anti-PD-L1 mAb. These observations suggest that anti-PD-L1 mAb treatment adds ADCC activity to the cytotoxicity of γδ T cells itself against PD-L1high cancer cells. The present results suggest that ex vivo expanded γδ T cells have antitumor activity independently of PD-L1 expression and may be promising effector cells for γδ T cell immunotherapy.
抄録:

英語フィールド

Author:
*Mako Tomogane, Yusuke Sano, Daiki Shimizu, Teruki Shimizu, Masatsugu Miyashita, Yuki Toda, Shigekuni Hosogi, Yoshimasa Tanaka, Shinya Kimura, Eishi Ashihara
Title:
Human Vγ9Vδ2 T cells exert anti-tumor activity independently of PD-L1 expression in tumor cells
Announcement information:
Biochem Biophys Res Commun Vol: 573 Page: 132-139
Keyword:
PD-1; PD-L1; RNA interference; Vγ9Vδ2 T cell; γδ T cell
An abstract:
Human γδ T cells expressing Vγ9Vδ2 T cell receptors play a crucial role in the innate immune system and have an attracted interest as effector cells in adoptive cellular immunotherapy. However, the efficacy of adoptive cellular immunotherapy for the treatment of tumors requires overcoming the immunosuppressive microenvironment. αβ T cell inhibition in the tumor microenvironment is associated with programmed death-ligand 1 (PD-L1) expression level. Vγ9Vδ2 T cells (abbreviated as γδ T cells here) exert potent cytotoxic effects in various cancers; however, γδ T cell activity in relation to the level of PD-L1 expression in cancer cells remains unclear, and the association between the PD-1/PD-L1 axis and γδ T cell cytotoxicity needs to be investigated. In this study, PD-1 blockade did not increase the cytotoxicity of γδ T cells against PD-L1high cancer cells. However, the anti-PD-L1 monoclonal antibody (mAb) enhanced the cytotoxicity of γδ T cells against a subset of cancer cells, whereas PD-L1 knockdown did not increase the cytotoxicity of γδ T cells. We also found that the expression levels of PD-L1 were positively correlated with the changes of γδ T cells cytotoxicity induced by anti-PD-L1 mAb. These observations suggest that anti-PD-L1 mAb treatment adds ADCC activity to the cytotoxicity of γδ T cells itself against PD-L1high cancer cells. The present results suggest that ex vivo expanded γδ T cells have antitumor activity independently of PD-L1 expression and may be promising effector cells for γδ T cell immunotherapy.


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