Imiquimod Exerts Antitumor Effects by Inducing Immunogenic Cell Death and Is Enhanced by the Glycolytic Inhibitor 2-Deoxyglucose

doi:10.1016/j.jid.2019.12.039

中山醫學大學機構典藏 CSMUIR > 中山醫學大學研究成果 > 期刊論文 > Item 310902500/24867

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/24867

Title:	Imiquimod Exerts Antitumor Effects by Inducing Immunogenic Cell Death and Is Enhanced by the Glycolytic Inhibitor 2-Deoxyglucose
Authors:	Huang, SW;Wang, ST;Chang, SH;Chuang, KC;Wang, HY;Kao, JK;Liang, SM;Wu, CY;Kao, SH;Chen, YJ;Shieh, JJ
Date:	2020
Issue Date:	2022-08-09T08:09:17Z (UTC)
Publisher:	ELSEVIER SCIENCE INC
ISSN:	0022-202X
Abstract:	The induction of immunogenic cell death (ICD) in cancer cells triggers specific immune responses against the same cancer cells. Imiquimod (IMQ) is a synthetic ligand of toll-like receptor 7 that exerts antitumor activity by stimulating cell-mediated immunity or by directly inducing apoptosis. Whether IMQ causes tumors to undergo ICD and elicits a specific antitumor immune response is unknown. We demonstrated that IMQ-induced ICD-associated features, including the surface exposure of calreticulin and the secretion of adenosine triphosphate and HMGB1, were mediated by ROS and endoplasmic reticulum stress. In a B16F10 melanoma mouse model, vaccinating mice with IMQ-induced ICD cell lysate or directly injecting IMQ in situ reduced tumor growth that was mediated by inducing tumor-specific T-cell proliferation, promoting tumor-specific cytotoxic killing by CD8(+) T cells, and increasing the infiltration of various immune cells into tumor lesions. The ICD-associated features were crucial in the induction of specific antitumor immunity in vivo. The glycolytic inhibitor 2-deoxyglucose enhanced IMQ-induced ICD-associated features and strengthened the antitumor immunity mediated by IMQ-induced ICD cell lysate in p53-mutant cancer cells, which were IMQ-resistant in vitro. We conclude that IMQ is an authentic ICD inducer and provide a concept connecting IMQ-induced cancer cell death and antitumor immune responses.
URI:	http://dx.doi.org/10.1016/j.jid.2019.12.039 https://www.webofscience.com/wos/woscc/full-record/WOS:000560076300004 https://ir.csmu.edu.tw:8080/handle/310902500/24867
Relation:	JOURNAL OF INVESTIGATIVE DERMATOLOGY ,2020 ,v140 ,issue 9 ,p1771-+
Appears in Collections:	[中山醫學大學研究成果] 期刊論文

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