Interleukin‐33 as an early predictor of cetuximab treatment efficacy in patients with colorectal cancer

Abstract Background Cetuximab is used for colorectal cancer (CRC) treatment. However, the early biomarker of treatment efficacy of cetuximab has not been identified. Methods After 1 year of cetuximab treatment, patients were divided into an effective group and an ineffective group. The interleukin‐3...

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Autores principales:	Xujun Zhang, Kefan Bi, Xiaoxuan Tu, Qiong Zhang, Qingyi Cao, Yan Liang, Ping Zeng, Lin Wang, Tianxing Liu, Weijia Fang, Hongyan Diao
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	cetuximab colorectal cancer IL‐33 NK cell Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/a90dc28a276847e28e408e853d44edcc
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spelling	oai:doaj.org-article:a90dc28a276847e28e408e853d44edcc2021-12-01T04:49:14ZInterleukin‐33 as an early predictor of cetuximab treatment efficacy in patients with colorectal cancer2045-763410.1002/cam4.4331https://doaj.org/article/a90dc28a276847e28e408e853d44edcc2021-12-01T00:00:00Zhttps://doi.org/10.1002/cam4.4331https://doaj.org/toc/2045-7634Abstract Background Cetuximab is used for colorectal cancer (CRC) treatment. However, the early biomarker of treatment efficacy of cetuximab has not been identified. Methods After 1 year of cetuximab treatment, patients were divided into an effective group and an ineffective group. The interleukin‐33 (IL‐33) level and the distribution of lymphatic cells in patients were investigated by analyzing the peripheral blood mononuclear cells via flow cytometry analysis and ELISA. The correlation between IL‐33 immunomodulatory effect and cetuximab treatment efficacy was determined through experiments in vivo and in vitro. Results The IL‐33 level in the peripheral blood was increased at 4 weeks after cetuximab administration of effective group, meanwhile, the osteopontin (OPN) was reduced. Whereas neither IL‐33 level nor OPN level of ineffective patients changed. In the effective group, the number of natural killer (NK) and CD8+ T cells were increased. Moreover, CD137 and CD107a expression on NK cells were higher in the effective group compared to the ineffective group. In vitro cetuximab treatment also increased the number of NK and CD8+ T cells as well as CD137 and CD107a expression upon IL‐33 stimulation. Moreover, the secretion of OPN was inhibited by IL‐33 administration in cetuximab‐treated PBMCs from the effective group patients. IL‐33 upregulated the cytotoxicity of NK cells and inhibited tumor cells growth in the effective cetuximab treatment mice. Conclusion Effective cetuximab treatment induced a change of IL‐33 and OPN at the early stage and triggered the NK cells antitumor activity. Consequently, significantly increased IL‐33 level and decreased OPN level in the peripheral blood at the early treatment are proposed as potential predictors of cetuximab treatment efficacy.Xujun ZhangKefan BiXiaoxuan TuQiong ZhangQingyi CaoYan LiangPing ZengLin WangTianxing LiuWeijia FangHongyan DiaoWileyarticlecetuximabcolorectal cancerIL‐33NK cellNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancer Medicine, Vol 10, Iss 23, Pp 8338-8351 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cetuximab colorectal cancer IL‐33 NK cell Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	cetuximab colorectal cancer IL‐33 NK cell Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Xujun Zhang Kefan Bi Xiaoxuan Tu Qiong Zhang Qingyi Cao Yan Liang Ping Zeng Lin Wang Tianxing Liu Weijia Fang Hongyan Diao Interleukin‐33 as an early predictor of cetuximab treatment efficacy in patients with colorectal cancer
description	Abstract Background Cetuximab is used for colorectal cancer (CRC) treatment. However, the early biomarker of treatment efficacy of cetuximab has not been identified. Methods After 1 year of cetuximab treatment, patients were divided into an effective group and an ineffective group. The interleukin‐33 (IL‐33) level and the distribution of lymphatic cells in patients were investigated by analyzing the peripheral blood mononuclear cells via flow cytometry analysis and ELISA. The correlation between IL‐33 immunomodulatory effect and cetuximab treatment efficacy was determined through experiments in vivo and in vitro. Results The IL‐33 level in the peripheral blood was increased at 4 weeks after cetuximab administration of effective group, meanwhile, the osteopontin (OPN) was reduced. Whereas neither IL‐33 level nor OPN level of ineffective patients changed. In the effective group, the number of natural killer (NK) and CD8+ T cells were increased. Moreover, CD137 and CD107a expression on NK cells were higher in the effective group compared to the ineffective group. In vitro cetuximab treatment also increased the number of NK and CD8+ T cells as well as CD137 and CD107a expression upon IL‐33 stimulation. Moreover, the secretion of OPN was inhibited by IL‐33 administration in cetuximab‐treated PBMCs from the effective group patients. IL‐33 upregulated the cytotoxicity of NK cells and inhibited tumor cells growth in the effective cetuximab treatment mice. Conclusion Effective cetuximab treatment induced a change of IL‐33 and OPN at the early stage and triggered the NK cells antitumor activity. Consequently, significantly increased IL‐33 level and decreased OPN level in the peripheral blood at the early treatment are proposed as potential predictors of cetuximab treatment efficacy.
format	article
author	Xujun Zhang Kefan Bi Xiaoxuan Tu Qiong Zhang Qingyi Cao Yan Liang Ping Zeng Lin Wang Tianxing Liu Weijia Fang Hongyan Diao
author_facet	Xujun Zhang Kefan Bi Xiaoxuan Tu Qiong Zhang Qingyi Cao Yan Liang Ping Zeng Lin Wang Tianxing Liu Weijia Fang Hongyan Diao
author_sort	Xujun Zhang
title	Interleukin‐33 as an early predictor of cetuximab treatment efficacy in patients with colorectal cancer
title_short	Interleukin‐33 as an early predictor of cetuximab treatment efficacy in patients with colorectal cancer
title_full	Interleukin‐33 as an early predictor of cetuximab treatment efficacy in patients with colorectal cancer
title_fullStr	Interleukin‐33 as an early predictor of cetuximab treatment efficacy in patients with colorectal cancer
title_full_unstemmed	Interleukin‐33 as an early predictor of cetuximab treatment efficacy in patients with colorectal cancer
title_sort	interleukin‐33 as an early predictor of cetuximab treatment efficacy in patients with colorectal cancer
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/a90dc28a276847e28e408e853d44edcc
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_version_	1718405742005846016

Interleukin‐33 as an early predictor of cetuximab treatment efficacy in patients with colorectal cancer

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