Multifaceted glycoadjuvant@AuNPs inhibits tumor metastasis through promoting T cell activation and remodeling tumor microenvironment

Abstarct Background Cytosine-phosphate-guanine (CpG) dinucleotides has been used as adjuvants for cancer immunotherapy. However, unmodified CpG are not very efficient in clinical trials. Glucose, ligand of C-type lectin receptors (CLRs), can promote DC maturation and antigen presentation, which is t...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Xiaojing Xu, Minfeng Gan, Youzhen Ge, Cheng Yi, Tianyun Feng, Mengjie Liu, Cenhao Wu, Xiang Chen, Weidong Zhang, Lixiang Zhao, Jun Zou
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Biotechnology TP248.13-248.65 Medical technology R855-855.5
Acceso en línea:	https://doaj.org/article/e62dcbe351e8489c9a20b4e15db96588
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:e62dcbe351e8489c9a20b4e15db96588
record_format	dspace
spelling	oai:doaj.org-article:e62dcbe351e8489c9a20b4e15db965882021-11-21T12:29:40ZMultifaceted glycoadjuvant@AuNPs inhibits tumor metastasis through promoting T cell activation and remodeling tumor microenvironment10.1186/s12951-021-01129-31477-3155https://doaj.org/article/e62dcbe351e8489c9a20b4e15db965882021-11-01T00:00:00Zhttps://doi.org/10.1186/s12951-021-01129-3https://doaj.org/toc/1477-3155Abstarct Background Cytosine-phosphate-guanine (CpG) dinucleotides has been used as adjuvants for cancer immunotherapy. However, unmodified CpG are not very efficient in clinical trials. Glucose, ligand of C-type lectin receptors (CLRs), can promote DC maturation and antigen presentation, which is the first step of induction of adaptive immune responses. Therefore, conjugation of type B CpG DNA to glucose-containing glycopolymers may enhance the therapeutic effects against tumor by CpG-based vaccine. Methods gCpG was developed by chemical conjugation of type B CpG DNA to glucose-containing glycopolymers. The therapeutic effects of gCpG-based vaccine were tested in both murine primary melanoma model and its metastasis model. Results gCpG based tumor vaccine inhibited both primary and metastasis of melanoma in mice which was dependent on CD8 + T cells and IFNγ. In tumor microenvironment, gCpG treatment increased Th1 and CTL infiltration, increased M1 macrophages, decreased Tregs and MDSCs populations, and promoted inflammatory milieu with enhanced secretion of IFNγ and TNFα. The anti-tumor efficacy of gCpG was dramatically enhanced when combined with anti-PD1 immunotherapy. Conclusions We confirmed that gCpG was a promising adjuvant for vaccine formulation by activating both tumor-specific Th1 and Tc1 responses, and regulating tumor microenvironments. Graphical AbstractXiaojing XuMinfeng GanYouzhen GeCheng YiTianyun FengMengjie LiuCenhao WuXiang ChenWeidong ZhangLixiang ZhaoJun ZouBMCarticleBiotechnologyTP248.13-248.65Medical technologyR855-855.5ENJournal of Nanobiotechnology, Vol 19, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biotechnology TP248.13-248.65 Medical technology R855-855.5
spellingShingle	Biotechnology TP248.13-248.65 Medical technology R855-855.5 Xiaojing Xu Minfeng Gan Youzhen Ge Cheng Yi Tianyun Feng Mengjie Liu Cenhao Wu Xiang Chen Weidong Zhang Lixiang Zhao Jun Zou Multifaceted glycoadjuvant@AuNPs inhibits tumor metastasis through promoting T cell activation and remodeling tumor microenvironment
description	Abstarct Background Cytosine-phosphate-guanine (CpG) dinucleotides has been used as adjuvants for cancer immunotherapy. However, unmodified CpG are not very efficient in clinical trials. Glucose, ligand of C-type lectin receptors (CLRs), can promote DC maturation and antigen presentation, which is the first step of induction of adaptive immune responses. Therefore, conjugation of type B CpG DNA to glucose-containing glycopolymers may enhance the therapeutic effects against tumor by CpG-based vaccine. Methods gCpG was developed by chemical conjugation of type B CpG DNA to glucose-containing glycopolymers. The therapeutic effects of gCpG-based vaccine were tested in both murine primary melanoma model and its metastasis model. Results gCpG based tumor vaccine inhibited both primary and metastasis of melanoma in mice which was dependent on CD8 + T cells and IFNγ. In tumor microenvironment, gCpG treatment increased Th1 and CTL infiltration, increased M1 macrophages, decreased Tregs and MDSCs populations, and promoted inflammatory milieu with enhanced secretion of IFNγ and TNFα. The anti-tumor efficacy of gCpG was dramatically enhanced when combined with anti-PD1 immunotherapy. Conclusions We confirmed that gCpG was a promising adjuvant for vaccine formulation by activating both tumor-specific Th1 and Tc1 responses, and regulating tumor microenvironments. Graphical Abstract
format	article
author	Xiaojing Xu Minfeng Gan Youzhen Ge Cheng Yi Tianyun Feng Mengjie Liu Cenhao Wu Xiang Chen Weidong Zhang Lixiang Zhao Jun Zou
author_facet	Xiaojing Xu Minfeng Gan Youzhen Ge Cheng Yi Tianyun Feng Mengjie Liu Cenhao Wu Xiang Chen Weidong Zhang Lixiang Zhao Jun Zou
author_sort	Xiaojing Xu
title	Multifaceted glycoadjuvant@AuNPs inhibits tumor metastasis through promoting T cell activation and remodeling tumor microenvironment
title_short	Multifaceted glycoadjuvant@AuNPs inhibits tumor metastasis through promoting T cell activation and remodeling tumor microenvironment
title_full	Multifaceted glycoadjuvant@AuNPs inhibits tumor metastasis through promoting T cell activation and remodeling tumor microenvironment
title_fullStr	Multifaceted glycoadjuvant@AuNPs inhibits tumor metastasis through promoting T cell activation and remodeling tumor microenvironment
title_full_unstemmed	Multifaceted glycoadjuvant@AuNPs inhibits tumor metastasis through promoting T cell activation and remodeling tumor microenvironment
title_sort	multifaceted glycoadjuvant@aunps inhibits tumor metastasis through promoting t cell activation and remodeling tumor microenvironment
publisher	BMC
publishDate	2021
url	https://doaj.org/article/e62dcbe351e8489c9a20b4e15db96588
work_keys_str_mv	AT xiaojingxu multifacetedglycoadjuvantaunpsinhibitstumormetastasisthroughpromotingtcellactivationandremodelingtumormicroenvironment AT minfenggan multifacetedglycoadjuvantaunpsinhibitstumormetastasisthroughpromotingtcellactivationandremodelingtumormicroenvironment AT youzhenge multifacetedglycoadjuvantaunpsinhibitstumormetastasisthroughpromotingtcellactivationandremodelingtumormicroenvironment AT chengyi multifacetedglycoadjuvantaunpsinhibitstumormetastasisthroughpromotingtcellactivationandremodelingtumormicroenvironment AT tianyunfeng multifacetedglycoadjuvantaunpsinhibitstumormetastasisthroughpromotingtcellactivationandremodelingtumormicroenvironment AT mengjieliu multifacetedglycoadjuvantaunpsinhibitstumormetastasisthroughpromotingtcellactivationandremodelingtumormicroenvironment AT cenhaowu multifacetedglycoadjuvantaunpsinhibitstumormetastasisthroughpromotingtcellactivationandremodelingtumormicroenvironment AT xiangchen multifacetedglycoadjuvantaunpsinhibitstumormetastasisthroughpromotingtcellactivationandremodelingtumormicroenvironment AT weidongzhang multifacetedglycoadjuvantaunpsinhibitstumormetastasisthroughpromotingtcellactivationandremodelingtumormicroenvironment AT lixiangzhao multifacetedglycoadjuvantaunpsinhibitstumormetastasisthroughpromotingtcellactivationandremodelingtumormicroenvironment AT junzou multifacetedglycoadjuvantaunpsinhibitstumormetastasisthroughpromotingtcellactivationandremodelingtumormicroenvironment
_version_	1718418978010824704

Multifaceted glycoadjuvant@AuNPs inhibits tumor metastasis through promoting T cell activation and remodeling tumor microenvironment

Ejemplares similares