A lipid-soluble extract of Pinellia pedatisecta Schott enhances antitumor T cell responses by restoring tumor-associated dendritic cell activation and maturation

doi:10.1016/j.jep.2019.111980

	A lipid-soluble extract of Pinellia pedatisecta Schott enhances antitumor T cell responses by restoring tumor-associated dendritic cell activation and maturation
	Wang, Yumeng 1,2; Huang, Haixia 1,2; Yao, Sheng 3; Li, Guiling 1,2; Xu, Congjian 1,2; Ye, Yang 3; Gui, Suiqi 1,2
刊名	JOURNAL OF ETHNOPHARMACOLOGY
	2019-09-15
卷号	241 页码:12
关键词	Pinellia pedatisecta extract (PE) Cervical cancer HPV+ tumor Tumor-associated dendritic cell (TADC) SOCS1 T cell immunity
ISSN号	0378-8741
DOI	10.1016/j.jep.2019.111980
通讯作者	Li, Guiling(guilingli@fudan.edu.cn)
英文摘要	Ethnopharmacological relevance: Pinellia pedatisecta Schott (PPS)is a traditional Chinese medicine functioning as reducing swelling and drying dampness. Pinellia pedatisecta Schott extract (PE) has been confirmed to suppress cervical tumor growth and modulate the antitumor CD4(+) T helper immunity towards Th1. Aims: To explore the roles of PE in modulating tumor-associated dendritic cell (TADC) activation and function. Methods: For in vivo studies, HPV+TC-1 mouse tumor models were conducted and treated with PE for 3 weeks (10 mg/kg/d or 20 mg/kg/day). The immune profiles of spleen, tumor-draining lymph nodes (TDLNs), tumor and serum were analyzed by flow cytometry and multiplexed bead-based immunoassay. For in vitro studies, TADCs were generated by tumor-conditioned medium and treated with PE solution. The maturation and function of TADCs were evaluated by flow cytometry, ELISA, mixed lymphocyte reaction (MLR) and cytotoxic T lymphocyte (CTL) assay. Furthermore, the effect of PE on SOCS1 pathway was examined by western blotting and real time PCR. Results: PE upregulated the expression of major histocompatibility complex class II (MHCII) and costimulatory molecules CD80 and CD86 on TADCs and promoted IL-12 secretion from TADCs. In addition, PE-treated TADCs promoted the proliferation of CD4(+) and CD8(+) T cells and induced the differentiation of IFN-gamma (+) CD4(+) and GZMB(+) CD8(+) T cells. PE-treated TADCs also elicited a more powerful antigen-specific cytotoxic T lymphocyte (CTL) response. Furthermore, PE treatment in vivo enhanced the proliferation, activated the functional ability (increased Ki67, CD137, GZMB or IFN-gamma, TNF-alpha expression) and reversed the exhaustion (impaired CD95 or PD-1 expression) of antitumor T cells. Mechanistically, PE inhibited SOCS1-restrained JAK2 activation in TADCs. Conclusions: PE efficiently restored the immature status of TADCs and enhanced their function as antigen-presenting cells to further elicit antitumor Th1 and CTL responses, suggesting that PE may be a potential immunomodulatory drug for cancer treatment.
资助项目	National Natural Sciences Foundation of China[81873124]
WOS关键词	IMMUNE-RESPONSES ; DOWN-REGULATION ; CANCER ; OPPORTUNITIES ; DYSFUNCTION ; SUPPRESSOR ; INDUCTION ; INNATE
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:000480374900027
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/289018]
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, Dept Integrat Western & Tradit Med, Obstet & Gynecol Hosp, 128 Shen Yang Rd, Shanghai 200090, Peoples R China 2.Fudan Univ, Shanghai Key Lab Female Reprod Endocrine Related, Shanghai 200011, 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,Huang, Haixia,Yao, Sheng,et al. A lipid-soluble extract of Pinellia pedatisecta Schott enhances antitumor T cell responses by restoring tumor-associated dendritic cell activation and maturation[J]. JOURNAL OF ETHNOPHARMACOLOGY,2019,241:12.
APA	Wang, Yumeng.,Huang, Haixia.,Yao, Sheng.,Li, Guiling.,Xu, Congjian.,...&Gui, Suiqi.(2019).A lipid-soluble extract of Pinellia pedatisecta Schott enhances antitumor T cell responses by restoring tumor-associated dendritic cell activation and maturation.JOURNAL OF ETHNOPHARMACOLOGY,241,12.
MLA	Wang, Yumeng,et al."A lipid-soluble extract of Pinellia pedatisecta Schott enhances antitumor T cell responses by restoring tumor-associated dendritic cell activation and maturation".JOURNAL OF ETHNOPHARMACOLOGY 241(2019):12.