PMID- 31733580
OWN - NLM
STAT- MEDLINE
DCOM- 20200603
LR  - 20221207
IS  - 1950-6007 (Electronic)
IS  - 0753-3322 (Linking)
VI  - 121
DP  - 2020 Jan
TI  - Sophoridine suppresses macrophage-mediated immunosuppression through TLR4/IRF3 
      pathway and subsequently upregulates CD8(+) T cytotoxic function against gastric 
      cancer.
PG  - 109636
LID - S0753-3322(19)35258-8 [pii]
LID - 10.1016/j.biopha.2019.109636 [doi]
AB  - Gastric cancer is one of the most common and deadly neoplasms with limited 
      effective treatments. The emergence of the immunotherapy has brought great 
      expectations for cancer patients. Sophoridine is extracted from the seeds of 
      sophora alopecuroides and has various pharmacological actions including 
      anti-tumor, anti-inflammatory, anti- arrhythmia and anti-virus. However, the 
      effect of Sophoridine on gastric cancer microenvironment immunity and its 
      underling mechanism remains poorly known. This study was aimed to investigate the 
      effect of Sophoridine on the polarization status of gastric tumor-associated 
      macrophages (TAMs) and its underlying mechanism. We isolated primary bone 
      marrow-derived macrophages (BMDMs) and primary CD8(+) T cells to perform 
      coculture assay. Sophoridine educated TAMs polarize to M1-TAMs and suppressed 
      M2-TAMs polarization through TLR4/IRF3 axis. Sophoridine-treated TAMs exhibited 
      stronger pro-inflammatory function through upregulation the expression of INOS, 
      IFN-beta and IL-12alpha, and downregulation the expression of Arg-1, CD206 and IL-10. 
      Sophoridine -primed TAMs increased the proliferation and cytotoxic function of 
      CD8(+) T by upregulating the expression of Granzyme-B, TNF-alpha and Perforin, and 
      downregulated the expression of CD8(+) T cells function exhaustion markers PD-1, 
      Tim-3 and Lag-3. Furthermore, Sophoridine inhibited the migration ability of 
      macrophage by decrease the CCR2 expression. Thus, Sophoridine acted on 
      macrophages and CD8(+) T cells to reshape gastric cancer immune microenvironment. 
      Our studies provided preclinical basis for clinical application of Sophoridine.
CI  - Copyright (c) 2019 The Author(s). Published by Elsevier Masson SAS.. All rights 
      reserved.
FAU - Zhuang, Haiwen
AU  - Zhuang H
AD  - Department of General Surgery, The First Affiliated Hospital of Soochow 
      University, Suzhou 215006, China; Division of Gastrointestinal Surgery, 
      Department of General Surgery, Huai'an Second People's Hospital, The Affiliated 
      Huai'an Hospital of Xuzhou Medical University, Huai'an, China.
FAU - Dai, Xudong
AU  - Dai X
AD  - Department of General Surgery, Lianshui County People's Hospital, Lianshui 
      people's hospital affiliated to kangda college of Nanjing medical university, 
      Huai'an, China.
FAU - Zhang, Xiaoyu
AU  - Zhang X
AD  - Division of Gastrointestinal Surgery, Department of General Surgery, Huai'an 
      Second People's Hospital, The Affiliated Huai'an Hospital of Xuzhou Medical 
      University, Huai'an, China.
FAU - Mao, Zhongqi
AU  - Mao Z
AD  - Department of General Surgery, The First Affiliated Hospital of Soochow 
      University, 899 Pinghai Road, Suzhou 215006, China. Electronic address: 
      maozhongqi31@hotmail.com.
FAU - Huang, Haijin
AU  - Huang H
AD  - Department of General Surgery, Hongze District People's Hospital, Hongze, China. 
      Electronic address: Huanghaijin_xke@163.com.
LA  - eng
PT  - Journal Article
DEP - 20191113
PL  - France
TA  - Biomed Pharmacother
JT  - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
JID - 8213295
RN  - 0 (Alkaloids)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Interferon Regulatory Factor-3)
RN  - 0 (Irf3 protein, mouse)
RN  - 0 (Quinolizines)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Matrines)
SB  - IM
MH  - Alkaloids/*pharmacology
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology
MH  - CD8-Positive T-Lymphocytes/*drug effects/metabolism
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - Down-Regulation/drug effects
MH  - Humans
MH  - Immune Tolerance/drug effects
MH  - Immunosuppression Therapy/methods
MH  - Interferon Regulatory Factor-3/*metabolism
MH  - Macrophages/*drug effects/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Quinolizines/*pharmacology
MH  - RAW 264.7 Cells
MH  - Signal Transduction/*drug effects
MH  - Stomach Neoplasms/*drug therapy/metabolism
MH  - Toll-Like Receptor 4/*metabolism
MH  - Tumor Microenvironment/drug effects
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Up-Regulation/drug effects
MH  - Matrines
OTO - NOTNLM
OT  - CD8(+) T cells
OT  - Gastric cancer
OT  - Sophoridine
OT  - TLR4/IRF3 pathway
OT  - Tumor-associated macrophages
EDAT- 2019/11/17 06:00
MHDA- 2020/06/04 06:00
CRDT- 2019/11/17 06:00
PHST- 2019/09/15 00:00 [received]
PHST- 2019/11/01 00:00 [revised]
PHST- 2019/11/01 00:00 [accepted]
PHST- 2019/11/17 06:00 [pubmed]
PHST- 2020/06/04 06:00 [medline]
PHST- 2019/11/17 06:00 [entrez]
AID - S0753-3322(19)35258-8 [pii]
AID - 10.1016/j.biopha.2019.109636 [doi]
PST - ppublish
SO  - Biomed Pharmacother. 2020 Jan;121:109636. doi: 10.1016/j.biopha.2019.109636. Epub 
      2019 Nov 13.