Strategies to Improve the Antitumor Effect of γδ T Cell Immunotherapy for Clinical Application
Human γδ T cells show potent cytotoxicity against various types of cancer cells in a major histocompatibility complex unrestricted manner. Phosphoantigens and nitrogen-containing bisphosphonates (N-bis) stimulate γδ T cells via interaction between the γδ T cell receptor (TCR) and butyrophilin subfam...
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doaj-99b2384da52d4ad1b8be06d200f26ba72021-08-26T13:53:14ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-01228910891010.3390/ijms22168910Strategies to Improve the Antitumor Effect of γδ T Cell Immunotherapy for Clinical ApplicationMasatsugu Miyashita0Teruki Shimizu1Eishi Ashihara2Osamu Ukimura3Department of Urology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, JapanDepartment of Urology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, JapanDepartment of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Kyoto 607-8414, JapanDepartment of Urology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, JapanHuman γδ T cells show potent cytotoxicity against various types of cancer cells in a major histocompatibility complex unrestricted manner. Phosphoantigens and nitrogen-containing bisphosphonates (N-bis) stimulate γδ T cells via interaction between the γδ T cell receptor (TCR) and butyrophilin subfamily 3 member A1 (BTN3A1) expressed on target cells. γδ T cell immunotherapy is classified as either in vivo or ex vivo according to the method of activation. Immunotherapy with activated γδ T cells is well tolerated; however, the clinical benefits are unsatisfactory. Therefore, the antitumor effects need to be increased. Administration of γδ T cells into local cavities might improve antitumor effects by increasing the effector-to-target cell ratio. Some anticancer and molecularly targeted agents increase the cytotoxicity of γδ T cells via mechanisms involving natural killer group 2 member D (NKG2D)-mediated recognition of target cells. Both the tumor microenvironment and cancer stem cells exert immunosuppressive effects via mechanisms that include inhibitory immune checkpoint molecules. Therefore, co-immunotherapy with γδ T cells plus immune checkpoint inhibitors is a strategy that may improve cytotoxicity. The use of a bispecific antibody and chimeric antigen receptor might be effective to overcome current therapeutic limitations. Such strategies should be tested in a clinical research setting.https://www.mdpi.com/1422-0067/22/16/8910γδ T cellsimmunotherapytumor resistancecombination therapytumor microenvironmentimmune checkpoint inhibitor |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Masatsugu Miyashita Teruki Shimizu Eishi Ashihara Osamu Ukimura |
spellingShingle |
Masatsugu Miyashita Teruki Shimizu Eishi Ashihara Osamu Ukimura Strategies to Improve the Antitumor Effect of γδ T Cell Immunotherapy for Clinical Application International Journal of Molecular Sciences γδ T cells immunotherapy tumor resistance combination therapy tumor microenvironment immune checkpoint inhibitor |
author_facet |
Masatsugu Miyashita Teruki Shimizu Eishi Ashihara Osamu Ukimura |
author_sort |
Masatsugu Miyashita |
title |
Strategies to Improve the Antitumor Effect of γδ T Cell Immunotherapy for Clinical Application |
title_short |
Strategies to Improve the Antitumor Effect of γδ T Cell Immunotherapy for Clinical Application |
title_full |
Strategies to Improve the Antitumor Effect of γδ T Cell Immunotherapy for Clinical Application |
title_fullStr |
Strategies to Improve the Antitumor Effect of γδ T Cell Immunotherapy for Clinical Application |
title_full_unstemmed |
Strategies to Improve the Antitumor Effect of γδ T Cell Immunotherapy for Clinical Application |
title_sort |
strategies to improve the antitumor effect of γδ t cell immunotherapy for clinical application |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-08-01 |
description |
Human γδ T cells show potent cytotoxicity against various types of cancer cells in a major histocompatibility complex unrestricted manner. Phosphoantigens and nitrogen-containing bisphosphonates (N-bis) stimulate γδ T cells via interaction between the γδ T cell receptor (TCR) and butyrophilin subfamily 3 member A1 (BTN3A1) expressed on target cells. γδ T cell immunotherapy is classified as either in vivo or ex vivo according to the method of activation. Immunotherapy with activated γδ T cells is well tolerated; however, the clinical benefits are unsatisfactory. Therefore, the antitumor effects need to be increased. Administration of γδ T cells into local cavities might improve antitumor effects by increasing the effector-to-target cell ratio. Some anticancer and molecularly targeted agents increase the cytotoxicity of γδ T cells via mechanisms involving natural killer group 2 member D (NKG2D)-mediated recognition of target cells. Both the tumor microenvironment and cancer stem cells exert immunosuppressive effects via mechanisms that include inhibitory immune checkpoint molecules. Therefore, co-immunotherapy with γδ T cells plus immune checkpoint inhibitors is a strategy that may improve cytotoxicity. The use of a bispecific antibody and chimeric antigen receptor might be effective to overcome current therapeutic limitations. Such strategies should be tested in a clinical research setting. |
topic |
γδ T cells immunotherapy tumor resistance combination therapy tumor microenvironment immune checkpoint inhibitor |
url |
https://www.mdpi.com/1422-0067/22/16/8910 |
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