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Antitumor and immunomodulatory effects of a novel multitarget inhibitor, CS2164, in mouse hepatocellular carcinoma models

As a novel orally active multitarget small molecule inhibitor, CS2164 has shown broad antitumor activities against several human tumor xenograft models in immune-compromised mice. However, the ability of CS2164 to modulate antitumor immunity in an immune-competent mouse tumor model remains undefined...

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Autores principales: Zhou, You, Fu, Chao, Kong, Yidi, Pan, Desi, Wang, Yanan, Huang, Shengjian, Li, Zhibin, Ning, Zhiqiang, Lu, Xianping, Shan, Song, Xin, Lijun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6749973/
https://www.ncbi.nlm.nih.gov/pubmed/30998512
http://dx.doi.org/10.1097/CAD.0000000000000791
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author Zhou, You
Fu, Chao
Kong, Yidi
Pan, Desi
Wang, Yanan
Huang, Shengjian
Li, Zhibin
Ning, Zhiqiang
Lu, Xianping
Shan, Song
Xin, Lijun
author_facet Zhou, You
Fu, Chao
Kong, Yidi
Pan, Desi
Wang, Yanan
Huang, Shengjian
Li, Zhibin
Ning, Zhiqiang
Lu, Xianping
Shan, Song
Xin, Lijun
author_sort Zhou, You
collection PubMed
description As a novel orally active multitarget small molecule inhibitor, CS2164 has shown broad antitumor activities against several human tumor xenograft models in immune-compromised mice. However, the ability of CS2164 to modulate antitumor immunity in an immune-competent mouse tumor model remains undefined, although antiangiogenic treatment has been reported to affect immune cell infiltration and remodel the tumor immune microenvironment. In the present study, the subcutaneous and ascites hepatocellular carcinoma (HCC) models in syngeneic Balb/c mice established by inoculation of an H22 hepatoma cell line were utilized to investigate the antitumor and immunomodulatory effects of CS2164. Although the antitumor effects of CS2164 were validated in both subcutaneous and ascites HCC models in syngeneic mice, CS2164 treatment consistently modulated immune cell populations, both in the periphery and in tumor microenvironments, with upregulation of CD4(+) and CD8(+) T cells in the spleen, but downregulation of immunosuppressive populations including regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages in the spleen and tumor tissues. Furthermore, CS2164 increased the relative gene expression and protein production of several proinflammatory cytokines in tumor-related ascites. These results indicate that CS2164 exerts an antitumor effect associated with its immunomodulatory activities in mouse HCC models, and may also provide evidence for the immunotherapy potentiation of CS2164 in future cancer treatment.
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spelling pubmed-67499732019-10-07 Antitumor and immunomodulatory effects of a novel multitarget inhibitor, CS2164, in mouse hepatocellular carcinoma models Zhou, You Fu, Chao Kong, Yidi Pan, Desi Wang, Yanan Huang, Shengjian Li, Zhibin Ning, Zhiqiang Lu, Xianping Shan, Song Xin, Lijun Anticancer Drugs Preclinical Reports As a novel orally active multitarget small molecule inhibitor, CS2164 has shown broad antitumor activities against several human tumor xenograft models in immune-compromised mice. However, the ability of CS2164 to modulate antitumor immunity in an immune-competent mouse tumor model remains undefined, although antiangiogenic treatment has been reported to affect immune cell infiltration and remodel the tumor immune microenvironment. In the present study, the subcutaneous and ascites hepatocellular carcinoma (HCC) models in syngeneic Balb/c mice established by inoculation of an H22 hepatoma cell line were utilized to investigate the antitumor and immunomodulatory effects of CS2164. Although the antitumor effects of CS2164 were validated in both subcutaneous and ascites HCC models in syngeneic mice, CS2164 treatment consistently modulated immune cell populations, both in the periphery and in tumor microenvironments, with upregulation of CD4(+) and CD8(+) T cells in the spleen, but downregulation of immunosuppressive populations including regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages in the spleen and tumor tissues. Furthermore, CS2164 increased the relative gene expression and protein production of several proinflammatory cytokines in tumor-related ascites. These results indicate that CS2164 exerts an antitumor effect associated with its immunomodulatory activities in mouse HCC models, and may also provide evidence for the immunotherapy potentiation of CS2164 in future cancer treatment. Lippincott Williams & Wilkins 2019-10 2019-09-13 /pmc/articles/PMC6749973/ /pubmed/30998512 http://dx.doi.org/10.1097/CAD.0000000000000791 Text en Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (http://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Preclinical Reports
Zhou, You
Fu, Chao
Kong, Yidi
Pan, Desi
Wang, Yanan
Huang, Shengjian
Li, Zhibin
Ning, Zhiqiang
Lu, Xianping
Shan, Song
Xin, Lijun
Antitumor and immunomodulatory effects of a novel multitarget inhibitor, CS2164, in mouse hepatocellular carcinoma models
title Antitumor and immunomodulatory effects of a novel multitarget inhibitor, CS2164, in mouse hepatocellular carcinoma models
title_full Antitumor and immunomodulatory effects of a novel multitarget inhibitor, CS2164, in mouse hepatocellular carcinoma models
title_fullStr Antitumor and immunomodulatory effects of a novel multitarget inhibitor, CS2164, in mouse hepatocellular carcinoma models
title_full_unstemmed Antitumor and immunomodulatory effects of a novel multitarget inhibitor, CS2164, in mouse hepatocellular carcinoma models
title_short Antitumor and immunomodulatory effects of a novel multitarget inhibitor, CS2164, in mouse hepatocellular carcinoma models
title_sort antitumor and immunomodulatory effects of a novel multitarget inhibitor, cs2164, in mouse hepatocellular carcinoma models
topic Preclinical Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6749973/
https://www.ncbi.nlm.nih.gov/pubmed/30998512
http://dx.doi.org/10.1097/CAD.0000000000000791
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