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Huaier Extractum Promotes Dendritic Cells Maturation and Favors them to Induce Th1 Immune Response: One of the Mechanisms Underlying Its Anti-Tumor Activity

Authors
  • Pan, Jun1, 2, 3
  • Jiang, Zhou1, 2, 3
  • Wu, Dang1, 4
  • Yang, Chenghui1, 2, 3
  • Wang, Zhen1, 2, 3
  • Huang, Jian1, 2, 3
  • 1 Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P. R. China
  • 2 Cancer Institute (Key Laboratory of Cancer Prevention & Intervention, National Ministry of Education), Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P. R. China
  • 3 Department of Breast Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P. R. China
  • 4 Department of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P. R. China
Type
Published Article
Journal
Integrative Cancer Therapies
Publisher
SAGE Publications
Publication Date
Oct 15, 2020
Volume
19
Identifiers
DOI: 10.1177/1534735420946830
PMID: 33054422
PMCID: PMC7570295
Source
PubMed Central
Keywords
License
Unknown

Abstract

Huaier, a sandy beige mushroom with anti-tumor effects, has been applied into Traditional Chinese Medicine for more than 1600 years. Previous studies showed that Huaier exerted its anti-tumor effects not only by direct action on tumor cells, but also indirectly by modulation of immune function. In the present study, we found that Huaier treatment significantly repressed tumor growth in mice with 4T1 breast cancer and resulted in significant accumulation of CD4+ T cells and mature dendritic cells (DCs) in the tumor microenvironment. In vitro experiments demonstrated that Huaier treatment promoted both DC2.4 and bone marrow derived DCs (BMDCs) to express costimulatory molecules, enhance production of IL-1β and IL-12p70, while it inhibited their phagocytic activities, suggesting that Huaier treatment promotes maturation of DCs. Furthermore, we found Huaier-treated DCs profoundly stimulated proliferation of alloreactive CD4+ T cells and drove them to differentiate into Th1 subset. Expression of PI3K, Akt, p-Akt, JNK, and p-JNK was up-regulated, while p-p38 MAPK was down-regulated in Huaier-treated BMDCs, suggesting that Huaier promotes maturation of DCs with potent ability to activate Th1 immune response via modulation of MAPK and PI3K/Akt signaling pathways. Our findings provide further evidence for the mechanisms underlying the anti-tumor activity of Huaier.

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