Valproic Acid-Like Compounds Enhance and Prolong the Radiotherapy Effect on Breast Cancer by Activating and Maintaining Anti-Tumor Immune Function.

Cai, Z; Lim, D; Liu, G; Chen, C; Jin, L; Duan, W; Ding, C; Sun, Q; Peng, J; Dong, C; Zhang, F; Feng, Z

Valproic Acid-Like Compounds Enhance and Prolong the Radiotherapy Effect on Breast Cancer by Activating and Maintaining Anti-Tumor Immune Function.

Cai, Z Lim, D Liu, G Chen, C Jin, L Duan, W Ding, C Sun, Q Peng, J Dong, C Zhang, F Feng, Z

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Publisher:: FRONTIERS MEDIA SA
Publication Type:: Journal Article
Citation:: Front Immunol, 2021, 12, pp. 646384
Issue Date:: 2021

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Field	Value	Language
dc.contributor.author	Cai, Z
dc.contributor.author	Lim, D
dc.contributor.author	Liu, G
dc.contributor.author	Chen, C
dc.contributor.author	Jin, L
dc.contributor.author	Duan, W
dc.contributor.author	Ding, C
dc.contributor.author	Sun, Q
dc.contributor.author	Peng, J
dc.contributor.author	Dong, C
dc.contributor.author	Zhang, F
dc.contributor.author	Feng, Z
dc.date.accessioned	2024-09-03T23:28:39Z
dc.date.available	2021-04-16
dc.date.available	2024-09-03T23:28:39Z
dc.date.issued	2021
dc.identifier.citation	Front Immunol, 2021, 12, pp. 646384
dc.identifier.issn	1664-3224
dc.identifier.issn	1664-3224
dc.identifier.uri	http://hdl.handle.net/10453/180596
dc.description.abstract	Inadequate sustained immune activation and tumor recurrence are major limitations of radiotherapy (RT), sustained and targeted activation of the tumor microenvironment can overcome this obstacle. Here, by two models of a primary rat breast cancer and cell co-culture, we demonstrated that valproic acid (VPA) and its derivative (HPTA) are effective immune activators for RT to inhibit tumor growth by inducing myeloid-derived macrophages and polarizing them toward the M1 phenotype, thus elevate the expression of cytokines such as IL-12, IL-6, IFN-γ and TNF-α during the early stage of the combination treatment. Meanwhile, activated CD8+ T cells increased, angiogenesis of tumors is inhibited, and the vasculature becomes sparse. Furthermore, it was suggested that VPA/HPTA can enhance the effects of RT via macrophage-mediated and macrophage-CD8+ T cell-mediated anti-tumor immunity. The combination of VPA/HPTA and RT treatment slowed the growth of tumors and prolong the anti-tumor effect by continuously maintaining the activated immune response. These are promising findings for the development of new effective, low-cost concurrent cancer therapy.
dc.format	Electronic-eCollection
dc.language	eng
dc.publisher	FRONTIERS MEDIA SA
dc.relation.ispartof	Front Immunol
dc.relation.isbasedon	10.3389/fimmu.2021.646384
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	1107 Immunology, 1108 Medical Microbiology
dc.subject.classification	3101 Biochemistry and cell biology
dc.subject.classification	3105 Genetics
dc.subject.classification	3204 Immunology
dc.subject.mesh	Animals
dc.subject.mesh	Breast Neoplasms
dc.subject.mesh	CD8-Positive T-Lymphocytes
dc.subject.mesh	Cytokines
dc.subject.mesh	Female
dc.subject.mesh	Humans
dc.subject.mesh	Immunity
dc.subject.mesh	Macrophage Activation
dc.subject.mesh	Macrophages
dc.subject.mesh	Radiation Tolerance
dc.subject.mesh	Rats, Sprague-Dawley
dc.subject.mesh	Signal Transduction
dc.subject.mesh	Tumor Microenvironment
dc.subject.mesh	Valproic Acid
dc.subject.mesh	Rats
dc.subject.mesh	CD8-Positive T-Lymphocytes
dc.subject.mesh	Macrophages
dc.subject.mesh	Animals
dc.subject.mesh	Humans
dc.subject.mesh	Rats
dc.subject.mesh	Rats, Sprague-Dawley
dc.subject.mesh	Breast Neoplasms
dc.subject.mesh	Valproic Acid
dc.subject.mesh	Cytokines
dc.subject.mesh	Signal Transduction
dc.subject.mesh	Immunity
dc.subject.mesh	Macrophage Activation
dc.subject.mesh	Radiation Tolerance
dc.subject.mesh	Female
dc.subject.mesh	Tumor Microenvironment
dc.subject.mesh	Animals
dc.subject.mesh	Breast Neoplasms
dc.subject.mesh	CD8-Positive T-Lymphocytes
dc.subject.mesh	Cytokines
dc.subject.mesh	Female
dc.subject.mesh	Humans
dc.subject.mesh	Immunity
dc.subject.mesh	Macrophage Activation
dc.subject.mesh	Macrophages
dc.subject.mesh	Radiation Tolerance
dc.subject.mesh	Rats, Sprague-Dawley
dc.subject.mesh	Signal Transduction
dc.subject.mesh	Tumor Microenvironment
dc.subject.mesh	Valproic Acid
dc.subject.mesh	Rats
dc.title	Valproic Acid-Like Compounds Enhance and Prolong the Radiotherapy Effect on Breast Cancer by Activating and Maintaining Anti-Tumor Immune Function.
dc.type	Journal Article
utslib.citation.volume	12
utslib.location.activity	Switzerland
utslib.for	1107 Immunology
utslib.for	1108 Medical Microbiology
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
pubs.organisational-group	University of Technology Sydney/All Manual Groups
pubs.organisational-group	University of Technology Sydney/All Manual Groups/Improving Palliative, Aged and Chronic Care through Clinical Research and Translation (IMPACCT)
pubs.organisational-group	University of Technology Sydney/All Manual Groups/UTS Ageing Research Collaborative (UARC)
pubs.organisational-group	University of Technology Sydney/All Manual Groups/Digital, Virtual and AI in Health Collaborative (DVAIHC)
utslib.copyright.status	open_access	*
dc.rights.license	This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/
dc.date.updated	2024-09-03T23:28:28Z
pubs.publication-status	Published online
pubs.volume	12

Abstract:

Inadequate sustained immune activation and tumor recurrence are major limitations of radiotherapy (RT), sustained and targeted activation of the tumor microenvironment can overcome this obstacle. Here, by two models of a primary rat breast cancer and cell co-culture, we demonstrated that valproic acid (VPA) and its derivative (HPTA) are effective immune activators for RT to inhibit tumor growth by inducing myeloid-derived macrophages and polarizing them toward the M1 phenotype, thus elevate the expression of cytokines such as IL-12, IL-6, IFN-γ and TNF-α during the early stage of the combination treatment. Meanwhile, activated CD8+ T cells increased, angiogenesis of tumors is inhibited, and the vasculature becomes sparse. Furthermore, it was suggested that VPA/HPTA can enhance the effects of RT via macrophage-mediated and macrophage-CD8+ T cell-mediated anti-tumor immunity. The combination of VPA/HPTA and RT treatment slowed the growth of tumors and prolong the anti-tumor effect by continuously maintaining the activated immune response. These are promising findings for the development of new effective, low-cost concurrent cancer therapy.

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http://hdl.handle.net/10453/180596