Antitumor Effect of Korean Red Ginseng through Blockade of PD-1/PD-L1 Interaction in a Humanized PD-L1 Knock-In MC38 Cancer Mouse Model
Blocking immune checkpoints, programmed death-1 (PD-1) and its ligand PD-L1, has proven a promising anticancer strategy for enhancing cytotoxic T cell activity. Although we previously demonstrated that ginsenoside Rg3, Rh2, and compound K block the interaction of PD-1 and PD-L1, the antitumor effect...
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MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/3/1894 |
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| author | Eun-Ji Lee Ju-Hye Yang Hye Jin Yang Chong-Kwan Cho Jang-Gi Choi Hwan-Suck Chung |
| author_facet | Eun-Ji Lee Ju-Hye Yang Hye Jin Yang Chong-Kwan Cho Jang-Gi Choi Hwan-Suck Chung |
| author_sort | Eun-Ji Lee |
| collection | DOAJ |
| description | Blocking immune checkpoints, programmed death-1 (PD-1) and its ligand PD-L1, has proven a promising anticancer strategy for enhancing cytotoxic T cell activity. Although we previously demonstrated that ginsenoside Rg3, Rh2, and compound K block the interaction of PD-1 and PD-L1, the antitumor effect through blockade of this interaction by Korean Red Ginseng alone is unknown. Therefore, we determined the effects of Korean Red Ginseng extract (RGE) on the PD-1/PD-L1 interaction and its antitumor effects using a humanized PD-1/PD-L1-expressing colorectal cancer (CRC) mouse model. RGE significantly blocked the interaction between human PD-1 and PD-L1 in a competitive ELISA. The CD8<sup>+</sup> T cell-mediated tumor cell killing effect of RGE was evaluated using murine hPD-L1-expressing MC38 cells and tumor-infiltrating hPD-1-expressing CD8<sup>+</sup> T cells isolated from hPD-L1 MC38 tumor-bearing hPD-1 mice. RGE also reduced the survival of hPD-L1 MC38 cells in a cell co-culture system using tumor-infiltrating CD8<sup>+</sup> T cells as effector cells combined with hPD-L1 MC38 target cells. RGE or Keytruda (positive control) treatment markedly suppressed the growth of hPD-L1 MC38 allograft tumors, increased CD8<sup>+</sup> T cell infiltration into tumors, and enhanced the production of Granzyme B. RGE exhibits anticancer effects through the PD-1/PD-L1 blockade, which warrants its further development as an immunotherapy. |
| first_indexed | 2024-03-11T09:42:55Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T09:42:55Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-86f86c3219124c6eaf8a75d3222417802023-11-16T16:49:16ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-01243189410.3390/ijms24031894Antitumor Effect of Korean Red Ginseng through Blockade of PD-1/PD-L1 Interaction in a Humanized PD-L1 Knock-In MC38 Cancer Mouse ModelEun-Ji Lee0Ju-Hye Yang1Hye Jin Yang2Chong-Kwan Cho3Jang-Gi Choi4Hwan-Suck Chung5Korean Medicine Application Center, Korea Institute of Oriental Medicine, Daegu 41062, Republic of KoreaKorean Medicine Application Center, Korea Institute of Oriental Medicine, Daegu 41062, Republic of KoreaKorean Medicine Application Center, Korea Institute of Oriental Medicine, Daegu 41062, Republic of KoreaEast-West Cancer Center, Daejeon Korean Medicine Hospital of Daejeon University, Daejeon 35235, Republic of KoreaKorean Medicine Application Center, Korea Institute of Oriental Medicine, Daegu 41062, Republic of KoreaKorean Medicine Application Center, Korea Institute of Oriental Medicine, Daegu 41062, Republic of KoreaBlocking immune checkpoints, programmed death-1 (PD-1) and its ligand PD-L1, has proven a promising anticancer strategy for enhancing cytotoxic T cell activity. Although we previously demonstrated that ginsenoside Rg3, Rh2, and compound K block the interaction of PD-1 and PD-L1, the antitumor effect through blockade of this interaction by Korean Red Ginseng alone is unknown. Therefore, we determined the effects of Korean Red Ginseng extract (RGE) on the PD-1/PD-L1 interaction and its antitumor effects using a humanized PD-1/PD-L1-expressing colorectal cancer (CRC) mouse model. RGE significantly blocked the interaction between human PD-1 and PD-L1 in a competitive ELISA. The CD8<sup>+</sup> T cell-mediated tumor cell killing effect of RGE was evaluated using murine hPD-L1-expressing MC38 cells and tumor-infiltrating hPD-1-expressing CD8<sup>+</sup> T cells isolated from hPD-L1 MC38 tumor-bearing hPD-1 mice. RGE also reduced the survival of hPD-L1 MC38 cells in a cell co-culture system using tumor-infiltrating CD8<sup>+</sup> T cells as effector cells combined with hPD-L1 MC38 target cells. RGE or Keytruda (positive control) treatment markedly suppressed the growth of hPD-L1 MC38 allograft tumors, increased CD8<sup>+</sup> T cell infiltration into tumors, and enhanced the production of Granzyme B. RGE exhibits anticancer effects through the PD-1/PD-L1 blockade, which warrants its further development as an immunotherapy.https://www.mdpi.com/1422-0067/24/3/1894immune checkpointPD-1/PD-L1 inhibitorKorean Red Ginsengcancer immunologyhumanized PD-1 mice |
| spellingShingle | Eun-Ji Lee Ju-Hye Yang Hye Jin Yang Chong-Kwan Cho Jang-Gi Choi Hwan-Suck Chung Antitumor Effect of Korean Red Ginseng through Blockade of PD-1/PD-L1 Interaction in a Humanized PD-L1 Knock-In MC38 Cancer Mouse Model International Journal of Molecular Sciences immune checkpoint PD-1/PD-L1 inhibitor Korean Red Ginseng cancer immunology humanized PD-1 mice |
| title | Antitumor Effect of Korean Red Ginseng through Blockade of PD-1/PD-L1 Interaction in a Humanized PD-L1 Knock-In MC38 Cancer Mouse Model |
| title_full | Antitumor Effect of Korean Red Ginseng through Blockade of PD-1/PD-L1 Interaction in a Humanized PD-L1 Knock-In MC38 Cancer Mouse Model |
| title_fullStr | Antitumor Effect of Korean Red Ginseng through Blockade of PD-1/PD-L1 Interaction in a Humanized PD-L1 Knock-In MC38 Cancer Mouse Model |
| title_full_unstemmed | Antitumor Effect of Korean Red Ginseng through Blockade of PD-1/PD-L1 Interaction in a Humanized PD-L1 Knock-In MC38 Cancer Mouse Model |
| title_short | Antitumor Effect of Korean Red Ginseng through Blockade of PD-1/PD-L1 Interaction in a Humanized PD-L1 Knock-In MC38 Cancer Mouse Model |
| title_sort | antitumor effect of korean red ginseng through blockade of pd 1 pd l1 interaction in a humanized pd l1 knock in mc38 cancer mouse model |
| topic | immune checkpoint PD-1/PD-L1 inhibitor Korean Red Ginseng cancer immunology humanized PD-1 mice |
| url | https://www.mdpi.com/1422-0067/24/3/1894 |
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