HDAC inhibitor HPTA initiates anti-tumor response by CXCL9/10-recruited CXCR3+CD4+T cells against PAHs carcinogenicity.

Chen, C; Lim, D; Cai, Z; Zhang, F; Liu, G; Dong, C; Feng, Z

HDAC inhibitor HPTA initiates anti-tumor response by CXCL9/10-recruited CXCR3+CD4+T cells against PAHs carcinogenicity.

Chen, C Lim, D Cai, Z Zhang, F Liu, G Dong, C Feng, Z

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Publisher:: PERGAMON-ELSEVIER SCIENCE LTD
Publication Type:: Journal Article
Citation:: Food Chem Toxicol, 2023, 176, (Cell Death Dis. 10 2019), pp. 113783
Issue Date:: 2023-06

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Field	Value	Language
dc.contributor.author	Chen, C
dc.contributor.author	Lim, D
dc.contributor.author	Cai, Z
dc.contributor.author	Zhang, F
dc.contributor.author	Liu, G
dc.contributor.author	Dong, C
dc.contributor.author	Feng, Z
dc.date.accessioned	2023-10-05T00:15:38Z
dc.date.available	2023-04-11
dc.date.available	2023-10-05T00:15:38Z
dc.date.issued	2023-06
dc.identifier.citation	Food Chem Toxicol, 2023, 176, (Cell Death Dis. 10 2019), pp. 113783
dc.identifier.issn	0278-6915
dc.identifier.issn	1873-6351
dc.identifier.uri	http://hdl.handle.net/10453/172501
dc.description.abstract	Polycyclic aromatic hydrocarbons (PAHs) exposure in food is closely associated with the occurrence and development of breast cancer, which may attribute to altered immunotoxicity and immune regulation. Currently, cancer immunotherapy aims to promote tumor-specific T cell responses, especially CD4+T helper cells (Th) for anti-tumor immunity. The histone deacetylase inhibitors (HDACis) are found to exert an anti-tumor effect by reshaping the tumor immune microenvironment, but the immune regulatory mechanism of HDACis in PAHs-induced breast tumor remains elusive. Here, using established breast cancer models induced by 7,12-dimethylbenz[a]anthracene (DMBA), a potent carcinogenic agent of PAH, the novel HDACi, 2-hexyl-4-pentylene acid (HPTA) exhibited anti-tumor effect by activating T lymphocytes immune function. HPTA recruited CXCR3+CD4+T cells into chemokines CXCL9/10-enriched tumor sites, and the increased secretion of CXCL9/10 was regulated by the NF-κB-mediated pathway. Furthermore, HPTA promoted Th1 differentiation and assisted cytotoxic CD8+T cells in the elimination of breast cancer cells. These findings support the proposition of HPTA as a potential therapeutic in the treatment of PAHs-induced carcinogenicity.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	PERGAMON-ELSEVIER SCIENCE LTD
dc.relation.ispartof	Food Chem Toxicol
dc.relation.isbasedon	10.1016/j.fct.2023.113783
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	0908 Food Sciences
dc.subject.classification	Food Science
dc.subject.classification	3006 Food sciences
dc.subject.classification	3214 Pharmacology and pharmaceutical sciences
dc.subject.mesh	Humans
dc.subject.mesh	Female
dc.subject.mesh	T-Lymphocytes
dc.subject.mesh	Polycyclic Aromatic Hydrocarbons
dc.subject.mesh	Histone Deacetylase Inhibitors
dc.subject.mesh	Breast Neoplasms
dc.subject.mesh	Carcinogens
dc.subject.mesh	Tumor Microenvironment
dc.subject.mesh	Chemokine CXCL9
dc.subject.mesh	Receptors, CXCR3
dc.subject.mesh	T-Lymphocytes
dc.subject.mesh	Humans
dc.subject.mesh	Breast Neoplasms
dc.subject.mesh	Carcinogens
dc.subject.mesh	Female
dc.subject.mesh	Receptors, CXCR3
dc.subject.mesh	Chemokine CXCL9
dc.subject.mesh	Histone Deacetylase Inhibitors
dc.subject.mesh	Tumor Microenvironment
dc.subject.mesh	Polycyclic Aromatic Hydrocarbons
dc.subject.mesh	Humans
dc.subject.mesh	Female
dc.subject.mesh	T-Lymphocytes
dc.subject.mesh	Polycyclic Aromatic Hydrocarbons
dc.subject.mesh	Histone Deacetylase Inhibitors
dc.subject.mesh	Breast Neoplasms
dc.subject.mesh	Carcinogens
dc.subject.mesh	Tumor Microenvironment
dc.subject.mesh	Chemokine CXCL9
dc.subject.mesh	Receptors, CXCR3
dc.title	HDAC inhibitor HPTA initiates anti-tumor response by CXCL9/10-recruited CXCR3+CD4+T cells against PAHs carcinogenicity.
dc.type	Journal Article
utslib.citation.volume	176
utslib.location.activity	England
utslib.for	0908 Food Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Health
pubs.organisational-group	/University of Technology Sydney/Faculty of Health/IMPACCT
utslib.copyright.status	closed_access	*
dc.date.updated	2023-10-05T00:15:36Z
pubs.issue	Cell Death Dis. 10 2019
pubs.publication-status	Published
pubs.volume	176
utslib.citation.issue	Cell Death Dis. 10 2019

Abstract:

Polycyclic aromatic hydrocarbons (PAHs) exposure in food is closely associated with the occurrence and development of breast cancer, which may attribute to altered immunotoxicity and immune regulation. Currently, cancer immunotherapy aims to promote tumor-specific T cell responses, especially CD4+T helper cells (Th) for anti-tumor immunity. The histone deacetylase inhibitors (HDACis) are found to exert an anti-tumor effect by reshaping the tumor immune microenvironment, but the immune regulatory mechanism of HDACis in PAHs-induced breast tumor remains elusive. Here, using established breast cancer models induced by 7,12-dimethylbenz[a]anthracene (DMBA), a potent carcinogenic agent of PAH, the novel HDACi, 2-hexyl-4-pentylene acid (HPTA) exhibited anti-tumor effect by activating T lymphocytes immune function. HPTA recruited CXCR3+CD4+T cells into chemokines CXCL9/10-enriched tumor sites, and the increased secretion of CXCL9/10 was regulated by the NF-κB-mediated pathway. Furthermore, HPTA promoted Th1 differentiation and assisted cytotoxic CD8+T cells in the elimination of breast cancer cells. These findings support the proposition of HPTA as a potential therapeutic in the treatment of PAHs-induced carcinogenicity.

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http://hdl.handle.net/10453/172501