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Bojungikki-Tang Improves Response to PD-L1 Immunotherapy by Regulating the Tumor Microenvironment in MC38 Tumor-Bearing Mice

Immune checkpoint blockage targeting PD-L1 has led to breakthroughs in cancer treatment. Although anti-PD-L1-based immunotherapy has been approved as standard therapy in various cancer types, its therapeutic efficacy in most colorectal cancers (CRC) is still limited due to the low response to immuno...

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Autores principales: Chun, Jaemoo, Park, Sang-Min, Yi, Jin-Mu, Ha, In Jin, Kang, Han Na, Jeong, Mi-Kyung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300825/
https://www.ncbi.nlm.nih.gov/pubmed/35873573
http://dx.doi.org/10.3389/fphar.2022.901563
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author Chun, Jaemoo
Park, Sang-Min
Yi, Jin-Mu
Ha, In Jin
Kang, Han Na
Jeong, Mi-Kyung
author_facet Chun, Jaemoo
Park, Sang-Min
Yi, Jin-Mu
Ha, In Jin
Kang, Han Na
Jeong, Mi-Kyung
author_sort Chun, Jaemoo
collection PubMed
description Immune checkpoint blockage targeting PD-L1 has led to breakthroughs in cancer treatment. Although anti-PD-L1-based immunotherapy has been approved as standard therapy in various cancer types, its therapeutic efficacy in most colorectal cancers (CRC) is still limited due to the low response to immunotherapy. Therefore, combining treatment with herbal medicines could be an alternative approach for treating CRC to overcome this limitation. Bojungikki-Tang (BJIKT), a herbal formula used in traditional Chinese medicine, clinically improves the quality of life for cancer patients and has been associated with antitumor and immune-modulating activities. However, the regulatory effect of BJIKT on the immune response in the tumor microenvironment remains largely uninvestigated. In this study, we verified the inhibitory effect of BJIKT on tumor growth and investigated the regulatory effect of combination therapy with BJIKT and anti-PD-L1 on antitumor immune responses in an MC38 CRC-bearing C57BL/6 mouse model. Immune profiling analysis by flow cytometry was used to characterize the exact cell types contributing to anticancer activities. Combination treatment with BJIKT and anti-PD-L1 therapy significantly suppressed tumor growth in MC38-bearing mice and increased the proportion of cytotoxic T lymphocytes and natural killer cells in tumor tissues. Furthermore, BJIKT suppressed the population of myeloid-derived suppressor cells, suggesting that this combination treatment effectively regulates the immunological function of T-cells by improving the tumor microenvironment. The herbal formula BJIKT can be a novel therapeutic option for improving anti-PD-L1-based immunotherapy in patients with CRC.
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spelling pubmed-93008252022-07-22 Bojungikki-Tang Improves Response to PD-L1 Immunotherapy by Regulating the Tumor Microenvironment in MC38 Tumor-Bearing Mice Chun, Jaemoo Park, Sang-Min Yi, Jin-Mu Ha, In Jin Kang, Han Na Jeong, Mi-Kyung Front Pharmacol Pharmacology Immune checkpoint blockage targeting PD-L1 has led to breakthroughs in cancer treatment. Although anti-PD-L1-based immunotherapy has been approved as standard therapy in various cancer types, its therapeutic efficacy in most colorectal cancers (CRC) is still limited due to the low response to immunotherapy. Therefore, combining treatment with herbal medicines could be an alternative approach for treating CRC to overcome this limitation. Bojungikki-Tang (BJIKT), a herbal formula used in traditional Chinese medicine, clinically improves the quality of life for cancer patients and has been associated with antitumor and immune-modulating activities. However, the regulatory effect of BJIKT on the immune response in the tumor microenvironment remains largely uninvestigated. In this study, we verified the inhibitory effect of BJIKT on tumor growth and investigated the regulatory effect of combination therapy with BJIKT and anti-PD-L1 on antitumor immune responses in an MC38 CRC-bearing C57BL/6 mouse model. Immune profiling analysis by flow cytometry was used to characterize the exact cell types contributing to anticancer activities. Combination treatment with BJIKT and anti-PD-L1 therapy significantly suppressed tumor growth in MC38-bearing mice and increased the proportion of cytotoxic T lymphocytes and natural killer cells in tumor tissues. Furthermore, BJIKT suppressed the population of myeloid-derived suppressor cells, suggesting that this combination treatment effectively regulates the immunological function of T-cells by improving the tumor microenvironment. The herbal formula BJIKT can be a novel therapeutic option for improving anti-PD-L1-based immunotherapy in patients with CRC. Frontiers Media S.A. 2022-07-06 /pmc/articles/PMC9300825/ /pubmed/35873573 http://dx.doi.org/10.3389/fphar.2022.901563 Text en Copyright © 2022 Chun, Park, Yi, Ha, Kang and Jeong. 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 Pharmacology
Chun, Jaemoo
Park, Sang-Min
Yi, Jin-Mu
Ha, In Jin
Kang, Han Na
Jeong, Mi-Kyung
Bojungikki-Tang Improves Response to PD-L1 Immunotherapy by Regulating the Tumor Microenvironment in MC38 Tumor-Bearing Mice
title Bojungikki-Tang Improves Response to PD-L1 Immunotherapy by Regulating the Tumor Microenvironment in MC38 Tumor-Bearing Mice
title_full Bojungikki-Tang Improves Response to PD-L1 Immunotherapy by Regulating the Tumor Microenvironment in MC38 Tumor-Bearing Mice
title_fullStr Bojungikki-Tang Improves Response to PD-L1 Immunotherapy by Regulating the Tumor Microenvironment in MC38 Tumor-Bearing Mice
title_full_unstemmed Bojungikki-Tang Improves Response to PD-L1 Immunotherapy by Regulating the Tumor Microenvironment in MC38 Tumor-Bearing Mice
title_short Bojungikki-Tang Improves Response to PD-L1 Immunotherapy by Regulating the Tumor Microenvironment in MC38 Tumor-Bearing Mice
title_sort bojungikki-tang improves response to pd-l1 immunotherapy by regulating the tumor microenvironment in mc38 tumor-bearing mice
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300825/
https://www.ncbi.nlm.nih.gov/pubmed/35873573
http://dx.doi.org/10.3389/fphar.2022.901563
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