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Scutellarin enhances anti-tumor immune responses by reducing TNFR2-expressing CD4+Foxp3+ regulatory T cells
Chen, Shaokui1; Li, Ruixin1; Chen, Yibo1; Chou, Chon Kit1; Zhang, Zhexuan2; Yang, Yang1; Liao, Ping1; Wang, Qingqing3; Chen, Xin1,4,5,6
2022-07-01
Source PublicationBiomedicine and Pharmacotherapy
ISSN0753-3322
Volume151
Abstract

One characteristic of tumor-associated CD4Foxp3 regulatory T cells (Tregs) is the high expression of tumor necrosis factor receptor type II (TNFR2), a receptor that mediates the decisive effect of tumor necrosis factor (TNF) in the activation and expansion of Tregs. There is increasing evidence that inhibition of TNFR2 can enhance anti-tumor immune responses. Therefore, we screened Chinese herbal extracts for their capacity to block TNF-TNFR2 interaction. The results showed that the treatment with a Chinese herb extract could inhibit TNFR2-induced biological responses in vitro, including the proliferation of TNFR2 Tregs. Our subsequent study led to the identification of flavonoid compound scutellarin was responsible for the activity. Our results showed that scutellarin is able to disrupt the interaction of TNF-TNFR2 and inhibited the phosphorylation of p38 MAPK, a down-stream signaling component of TNFR2. Importantly, in vivo scutellarin treatment markedly enhanced the efficacy of tumor immunotherapy with CpG oligodeoxynucleotide in mouse CT26 colon cancer model. This effect of scutellarin was associated with the reduction of the number of tumor-infiltrating TNFR2-expressing Tregs and increased tumor infiltration of interferon-γ–producing CD8 T cells. Our result also suggests that scutellarin or its analogs may be used as an adjuvant to enhance the anti-tumor effect of immunotherapeutic agent by eliminating TNFR2 Treg activity.

KeywordCancer Immunotherapy cd4+foxp3+ Regulatory t Cells Cpg Oligodeoxynucleotide Scutellarin Tumor Necrosis Factor Tumor Necrosis Factor Receptor Ii
DOI10.1016/j.biopha.2022.113187
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaResearch & Experimental Medicine ; Pharmacology & Pharmacy
WOS SubjectMedicine, Research & Experimental ; Pharmacology & Pharmacy
WOS IDWOS:000807569300004
Scopus ID2-s2.0-85131115128
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Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorChen, Xin
Affiliation1.Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macao Special Administrative Region of China, 999078, China
2.College of Science, Hunan University of Technology and Business, Changsha, 410205, China
3.Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, 310058, China
4.Department of Pharmaceutical Sciences, Faculty of Health Sciences, University of Macau, Macao Special Administrative Region of China, 999078, China
5.MoE Frontiers Science Center for Precision Oncology, University of Macau, Macao Special Administrative Region of China, 999078, China
6.Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, University of Macau, Macao Special Administrative Region of China, 999078, China
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences;  Faculty of Health Sciences;  University of Macau
Recommended Citation
GB/T 7714
Chen, Shaokui,Li, Ruixin,Chen, Yibo,et al. Scutellarin enhances anti-tumor immune responses by reducing TNFR2-expressing CD4+Foxp3+ regulatory T cells[J]. Biomedicine and Pharmacotherapy,2022,151.
APA Chen, Shaokui,Li, Ruixin,Chen, Yibo,Chou, Chon Kit,Zhang, Zhexuan,Yang, Yang,Liao, Ping,Wang, Qingqing,&Chen, Xin.(2022).Scutellarin enhances anti-tumor immune responses by reducing TNFR2-expressing CD4+Foxp3+ regulatory T cells.Biomedicine and Pharmacotherapy,151.
MLA Chen, Shaokui,et al."Scutellarin enhances anti-tumor immune responses by reducing TNFR2-expressing CD4+Foxp3+ regulatory T cells".Biomedicine and Pharmacotherapy 151(2022).
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