A lipid-soluble extract of Pinellia pedatisecta Schott orchestrates intratumoral dendritic cell-driven immune activation through SOCS1 signaling in cervical cancer

doi:10.1016/j.jep.2020.112837

	A lipid-soluble extract of Pinellia pedatisecta Schott orchestrates intratumoral dendritic cell-driven immune activation through SOCS1 signaling in cervical cancer
	Wang, Yumeng 1,2; Lu, Chong 1,2; Huang, Haixia 1,2; Yao, Sheng 3; Xu, Congjian 1,2; Ye, Yang 3; Gui, Suiqi 1,2; Li, Guiling 1,2
刊名	JOURNAL OF ETHNOPHARMACOLOGY
	2021-03-01
卷号	267 页码:10
关键词	Cervical cancer Tumor-associated dendritic cell (TADC) Suppressor of cytokine signaling-1 (SOCS1) JAK/STAT pathway Immunotherapy Traditional Chinese medicine
ISSN号	0378-8741
DOI	10.1016/j.jep.2020.112837
通讯作者	Li, Guiling(guilingli@fudan.edu.cn)
英文摘要	Ethnopharmacological relevance: Pinellia pedatisecta Schott extract (PE) is generated from Pinellia pedatisecta Schott, a traditional Chinese medicinal plant. PE suppresses cervical tumor growth and exhibits effects on dendritic cells (DCs) that lead to modulation of antitumor CD4(+) and CD8(+) responses. Aims: To explore the underlying mechanisms by which PE modulates tumor-associated dendritic cell (TADC) activation and function. Methods: DCs and TADCs were generated from murine bone marrow and exposed to PE solutions at different doses, as well as to repeated doses separated at different time intervals. Quantitative PCR, Western blot analysis, flow cytometry, and gene silencing were used to analyze the modulatory effects of PE on the SOCS1/JAK2/STAT pathways. Furthermore, we separated human cervical tumor-infiltrated DCs (TIDCs) and conducted an ex-vivo stimulation model to observe the effect of PE. For phenotypic analysis of cultured DCs and ex vivo human specimens, we used flow cytometry to detect the molecular markers associated with cell function. Results: In cultured TADCs and human cervical TIDCs, maturation- and functional markers (MHCII, CD80, CD83, CD86, and IL-12) were downregulated, whereas SOCS1 was upregulated. PE enhanced the expression of CD80, CD86, and IL-12 in cervical TIDCs, which induced increased expression of CD107a, GZMB, and perforin in CTLs, and furthermore induced apoptosis in a larger number of tumor cells. In cultured TADCs, PE downregulated SOCS1 expression and activated the phosphorylation of JAK2, STAT1, STAT4, and STAT5 in both dose- and time-dependent manners. The effects of PE upregulating MHCII, CD80, CD86, IL-12 on TADCs were blocked after SOCS1 silencing. Conclusions: In this study, PE restored the impaired function of cervical TIDCs, thereby eliciting further antitumor CTL responses. The effects of PE on TADCs were mediated through inhibition of SOCS1 and activation of downstream JAK2-STAT1/STAT4/STAT5 pathways. PE may be a potent and effective immunomodulatory drug for antitumor treatment via the blockade of SOCS1 signaling in DCs.
资助项目	National Natural Science Foundation of China[81873124]
WOS关键词	FATTY-ACIDS ; EXPRESSION ; STAT5 ; INNATE ; INHIBITION ; SUPPRESSORS ; MACROPHAGES ; NANOVACCINE ; MECHANISMS ; MATURATION
WOS研究方向	Plant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine
语种	英语
出版者	ELSEVIER IRELAND LTD
WOS记录号	WOS:000606373500005
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/295967]
专题	中国科学院上海药物研究所
通讯作者	Li, Guiling
作者单位	1.Fudan Univ, Shanghai Key Lab Female Reprod Endocrine Related, Shanghai 200011, Peoples R China 2.Fudan Univ, Obstet & Gynecol Hosp, Dept Integrat Western & Tradit Med, 128 Shen Yang Rd, Shanghai 200090, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Wang, Yumeng,Lu, Chong,Huang, Haixia,et al. A lipid-soluble extract of Pinellia pedatisecta Schott orchestrates intratumoral dendritic cell-driven immune activation through SOCS1 signaling in cervical cancer[J]. JOURNAL OF ETHNOPHARMACOLOGY,2021,267:10.
APA	Wang, Yumeng.,Lu, Chong.,Huang, Haixia.,Yao, Sheng.,Xu, Congjian.,...&Li, Guiling.(2021).A lipid-soluble extract of Pinellia pedatisecta Schott orchestrates intratumoral dendritic cell-driven immune activation through SOCS1 signaling in cervical cancer.JOURNAL OF ETHNOPHARMACOLOGY,267,10.
MLA	Wang, Yumeng,et al."A lipid-soluble extract of Pinellia pedatisecta Schott orchestrates intratumoral dendritic cell-driven immune activation through SOCS1 signaling in cervical cancer".JOURNAL OF ETHNOPHARMACOLOGY 267(2021):10.