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An inhibitor of programmed death ligand 1 enhances natural killer cell-mediated immunity against malignant melanoma cells
Since ionizing radiation has showed the dramatic effect to kill the cancer cells through direct DNA damage as well as triggering anti-cancer immune responses including induction of NKG2D ligands, it has used for long time to treat many cancer patients. However, it has been known that radiotherapy mi...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016313/ https://www.ncbi.nlm.nih.gov/pubmed/33793576 http://dx.doi.org/10.1371/journal.pone.0248870 |
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author | Lee, Young Shin Heo, Woong Choi, Ho-Jung Cho, Hae-Ryung Nam, Ji Ho Ki, Yong Gan Lee, Hong-Rae Son, Woo-Chang Park, You-Soo Kang, Chi-Dug Bae, Jaeho |
author_facet | Lee, Young Shin Heo, Woong Choi, Ho-Jung Cho, Hae-Ryung Nam, Ji Ho Ki, Yong Gan Lee, Hong-Rae Son, Woo-Chang Park, You-Soo Kang, Chi-Dug Bae, Jaeho |
author_sort | Lee, Young Shin |
collection | PubMed |
description | Since ionizing radiation has showed the dramatic effect to kill the cancer cells through direct DNA damage as well as triggering anti-cancer immune responses including induction of NKG2D ligands, it has used for long time to treat many cancer patients. However, it has been known that radiotherapy might promote the remnant cancer cells to escape immune system and metastasis. One of the suggested ways of immune evasion is induction of a ligand for programmed death-1 (PD-L1) in head and neck cancer, bladder cancer and lung cancer cells which engages the receptor, programmed death-1 (PD-1) in immune cells. PD-1/PD-L1 axis transduces the inhibitory signal and suppresses the adaptive immunity. However, their role in innate immunity remains poorly understood. Therefore, we investigated whether ionizing radiation could change the expression of PD-L1 in malignant melanoma cells and the receptor, programmed death-1 (PD-1), in NK-92 cells. Surface PD-L1 levels on melanoma cells were increased by ionizing radiation in a dose-independent manner but the level of PD-L1 was not changed significantly in NK-92 cells. Radiation-induced PD-L1 suppressed the activity of the NK-92 cells against melanoma cells despite of upregulation of NKG2D ligands. Furthermore, activated NK cells had high level of PD-1 and could not kill PD-L1+ melanoma cells effectively. When we used PD-L1 inhibitor or silenced PD-L1 gene, inhibited PD-1/PD-L1 axis reversed the activity of the suppressed NK cells. Through these results, we supposed that PD-1/PD-L1 blockade could enhance the immune responses of NK cells against melanoma cells after radiotherapy and might overcome the PD-L1 mediated radioresistance of cancer cells. |
format | Online Article Text |
id | pubmed-8016313 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-80163132021-04-08 An inhibitor of programmed death ligand 1 enhances natural killer cell-mediated immunity against malignant melanoma cells Lee, Young Shin Heo, Woong Choi, Ho-Jung Cho, Hae-Ryung Nam, Ji Ho Ki, Yong Gan Lee, Hong-Rae Son, Woo-Chang Park, You-Soo Kang, Chi-Dug Bae, Jaeho PLoS One Research Article Since ionizing radiation has showed the dramatic effect to kill the cancer cells through direct DNA damage as well as triggering anti-cancer immune responses including induction of NKG2D ligands, it has used for long time to treat many cancer patients. However, it has been known that radiotherapy might promote the remnant cancer cells to escape immune system and metastasis. One of the suggested ways of immune evasion is induction of a ligand for programmed death-1 (PD-L1) in head and neck cancer, bladder cancer and lung cancer cells which engages the receptor, programmed death-1 (PD-1) in immune cells. PD-1/PD-L1 axis transduces the inhibitory signal and suppresses the adaptive immunity. However, their role in innate immunity remains poorly understood. Therefore, we investigated whether ionizing radiation could change the expression of PD-L1 in malignant melanoma cells and the receptor, programmed death-1 (PD-1), in NK-92 cells. Surface PD-L1 levels on melanoma cells were increased by ionizing radiation in a dose-independent manner but the level of PD-L1 was not changed significantly in NK-92 cells. Radiation-induced PD-L1 suppressed the activity of the NK-92 cells against melanoma cells despite of upregulation of NKG2D ligands. Furthermore, activated NK cells had high level of PD-1 and could not kill PD-L1+ melanoma cells effectively. When we used PD-L1 inhibitor or silenced PD-L1 gene, inhibited PD-1/PD-L1 axis reversed the activity of the suppressed NK cells. Through these results, we supposed that PD-1/PD-L1 blockade could enhance the immune responses of NK cells against melanoma cells after radiotherapy and might overcome the PD-L1 mediated radioresistance of cancer cells. Public Library of Science 2021-04-01 /pmc/articles/PMC8016313/ /pubmed/33793576 http://dx.doi.org/10.1371/journal.pone.0248870 Text en © 2021 Lee et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Lee, Young Shin Heo, Woong Choi, Ho-Jung Cho, Hae-Ryung Nam, Ji Ho Ki, Yong Gan Lee, Hong-Rae Son, Woo-Chang Park, You-Soo Kang, Chi-Dug Bae, Jaeho An inhibitor of programmed death ligand 1 enhances natural killer cell-mediated immunity against malignant melanoma cells |
title | An inhibitor of programmed death ligand 1 enhances natural killer cell-mediated immunity against malignant melanoma cells |
title_full | An inhibitor of programmed death ligand 1 enhances natural killer cell-mediated immunity against malignant melanoma cells |
title_fullStr | An inhibitor of programmed death ligand 1 enhances natural killer cell-mediated immunity against malignant melanoma cells |
title_full_unstemmed | An inhibitor of programmed death ligand 1 enhances natural killer cell-mediated immunity against malignant melanoma cells |
title_short | An inhibitor of programmed death ligand 1 enhances natural killer cell-mediated immunity against malignant melanoma cells |
title_sort | inhibitor of programmed death ligand 1 enhances natural killer cell-mediated immunity against malignant melanoma cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016313/ https://www.ncbi.nlm.nih.gov/pubmed/33793576 http://dx.doi.org/10.1371/journal.pone.0248870 |
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