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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
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.
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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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