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Sanguisorbae Radix Suppresses Colorectal Tumor Growth Through PD-1/PD-L1 Blockade and Synergistic Effect With Pembrolizumab in a Humanized PD-L1-Expressing Colorectal Cancer Mouse Model
Immune checkpoints such as programmed death-1 (PD-1) have been proven as antitumor targets by enhancing cytotoxic T cell activity. All immune checkpoint blockades are antibody therapeutics that have large size and high affinity, as well as known immune-related side effects and low responses. To over...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8511399/ https://www.ncbi.nlm.nih.gov/pubmed/34659228 http://dx.doi.org/10.3389/fimmu.2021.737076 |
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author | Lee, Eun-Ji Kim, Ji Hye Kim, Tae In Kim, Yeon-Ji Pak, Malk Eun Jeon, Chang Hyun Park, Yeo Jin Li, Wei Kim, Young Soo Choi, Jang-Gi Chung, Hwan-Suck |
author_facet | Lee, Eun-Ji Kim, Ji Hye Kim, Tae In Kim, Yeon-Ji Pak, Malk Eun Jeon, Chang Hyun Park, Yeo Jin Li, Wei Kim, Young Soo Choi, Jang-Gi Chung, Hwan-Suck |
author_sort | Lee, Eun-Ji |
collection | PubMed |
description | Immune checkpoints such as programmed death-1 (PD-1) have been proven as antitumor targets by enhancing cytotoxic T cell activity. All immune checkpoint blockades are antibody therapeutics that have large size and high affinity, as well as known immune-related side effects and low responses. To overcome the limitation of antibody therapeutics, we have explored PD-1/PD-L1 (programmed death-ligand 1) blockades in traditional oriental medicine, which has a long history but has not yet studied PD-1/PD-L1 blockades. Sanguisorbae Radix extract (SRE) blocked PD-1 and PD-L1 binding in competitive ELISA. SRE effectively inhibited the PD-1/PD-L1 interaction, thereby improving T cell receptor (TCR) signaling and the NFAT-mediated luciferase activity of T cells. SRE treatment reduced tumor growth in the humanized PD-L1 MC38 cell allograft humanized PD-1 mouse model. Additionally, the combination of SRE and pembrolizumab (anti-PD-1 antibody) suppressed tumor growth and increased infiltrated cytotoxic T cells to a greater extent did either agent alone. This study showed that SRE alone has anticancer effects via PD-1/PD-L1 blockade and that the combination therapy of SRE and pembrolizumab has enhanced immuno-oncologic effects. |
format | Online Article Text |
id | pubmed-8511399 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85113992021-10-14 Sanguisorbae Radix Suppresses Colorectal Tumor Growth Through PD-1/PD-L1 Blockade and Synergistic Effect With Pembrolizumab in a Humanized PD-L1-Expressing Colorectal Cancer Mouse Model Lee, Eun-Ji Kim, Ji Hye Kim, Tae In Kim, Yeon-Ji Pak, Malk Eun Jeon, Chang Hyun Park, Yeo Jin Li, Wei Kim, Young Soo Choi, Jang-Gi Chung, Hwan-Suck Front Immunol Immunology Immune checkpoints such as programmed death-1 (PD-1) have been proven as antitumor targets by enhancing cytotoxic T cell activity. All immune checkpoint blockades are antibody therapeutics that have large size and high affinity, as well as known immune-related side effects and low responses. To overcome the limitation of antibody therapeutics, we have explored PD-1/PD-L1 (programmed death-ligand 1) blockades in traditional oriental medicine, which has a long history but has not yet studied PD-1/PD-L1 blockades. Sanguisorbae Radix extract (SRE) blocked PD-1 and PD-L1 binding in competitive ELISA. SRE effectively inhibited the PD-1/PD-L1 interaction, thereby improving T cell receptor (TCR) signaling and the NFAT-mediated luciferase activity of T cells. SRE treatment reduced tumor growth in the humanized PD-L1 MC38 cell allograft humanized PD-1 mouse model. Additionally, the combination of SRE and pembrolizumab (anti-PD-1 antibody) suppressed tumor growth and increased infiltrated cytotoxic T cells to a greater extent did either agent alone. This study showed that SRE alone has anticancer effects via PD-1/PD-L1 blockade and that the combination therapy of SRE and pembrolizumab has enhanced immuno-oncologic effects. Frontiers Media S.A. 2021-09-29 /pmc/articles/PMC8511399/ /pubmed/34659228 http://dx.doi.org/10.3389/fimmu.2021.737076 Text en Copyright © 2021 Lee, Kim, Kim, Kim, Pak, Jeon, Park, Li, Kim, Choi and Chung https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Lee, Eun-Ji Kim, Ji Hye Kim, Tae In Kim, Yeon-Ji Pak, Malk Eun Jeon, Chang Hyun Park, Yeo Jin Li, Wei Kim, Young Soo Choi, Jang-Gi Chung, Hwan-Suck Sanguisorbae Radix Suppresses Colorectal Tumor Growth Through PD-1/PD-L1 Blockade and Synergistic Effect With Pembrolizumab in a Humanized PD-L1-Expressing Colorectal Cancer Mouse Model |
title | Sanguisorbae Radix Suppresses Colorectal Tumor Growth Through PD-1/PD-L1 Blockade and Synergistic Effect With Pembrolizumab in a Humanized PD-L1-Expressing Colorectal Cancer Mouse Model |
title_full | Sanguisorbae Radix Suppresses Colorectal Tumor Growth Through PD-1/PD-L1 Blockade and Synergistic Effect With Pembrolizumab in a Humanized PD-L1-Expressing Colorectal Cancer Mouse Model |
title_fullStr | Sanguisorbae Radix Suppresses Colorectal Tumor Growth Through PD-1/PD-L1 Blockade and Synergistic Effect With Pembrolizumab in a Humanized PD-L1-Expressing Colorectal Cancer Mouse Model |
title_full_unstemmed | Sanguisorbae Radix Suppresses Colorectal Tumor Growth Through PD-1/PD-L1 Blockade and Synergistic Effect With Pembrolizumab in a Humanized PD-L1-Expressing Colorectal Cancer Mouse Model |
title_short | Sanguisorbae Radix Suppresses Colorectal Tumor Growth Through PD-1/PD-L1 Blockade and Synergistic Effect With Pembrolizumab in a Humanized PD-L1-Expressing Colorectal Cancer Mouse Model |
title_sort | sanguisorbae radix suppresses colorectal tumor growth through pd-1/pd-l1 blockade and synergistic effect with pembrolizumab in a humanized pd-l1-expressing colorectal cancer mouse model |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8511399/ https://www.ncbi.nlm.nih.gov/pubmed/34659228 http://dx.doi.org/10.3389/fimmu.2021.737076 |
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