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

Abstract：

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-γ+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-γ, TNF-α 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.

journal_name

J Ethnopharmacol

journal_title

Journal of ethnopharmacology

authors

Wang Y,Huang H,Yao S,Li G,Xu C,Ye Y,Gui S

doi

10.1016/j.jep.2019.111980

subject

Has Abstract

pub_date

2019-09-15 00:00:00

pages

111980

eissn

0378-8741

issn

1872-7573

pii

S0378-8741(19)31067-0

journal_volume

241

pub_type

杂志文章

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