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Anti-TNFR2 enhanced the antitumor activity of a new HMGN1/3M-052 stimulated dendritic cell vaccine in a mouse model of colon cancer

  1. Author:
    Zhu, Lan
    Zhang, Xiangyan
    Chen, Xin
    Yang,De
    Nie, Yujie
    Pan, Runsang
    Li, Linzhao
    Wang, Chenglv
    Gui, Huan
    Chen, Shuanghui
    Jing, Qianyu
    Wang, Mengjiao
    Nie, Yingjie

  2. Author Address

    School of Medicine, Guizhou University, Guiyang, 550025, China. Electronic address: 1984018394@qq.com., NHC Key Laboratory of Pulmonary Immunological Diseases, Guizhou Provincial People 39;s Hospital, Guiyang, 550002, China. Electronic address: zxy35762@126.com., State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR, 999078, China. Electronic address: xchen@umac.mo., Laboratory of Cancer Immunometabolism, Center for Cancer Research, National Cancer Institute at Frederick, NIH, Frederick, MD, USA. Electronic address: yangd@mail.nih.gov., NHC Key Laboratory of Pulmonary Immunological Diseases, Guizhou Provincial People 39;s Hospital, Guiyang, 550002, China. Electronic address: 1637541011@qq.com., Department of Pathophysiology, School of Basic Medicine, Guizhou Medical University, Guiyang, 550025, China. Electronic address: panrunsang@163.com., School of Medicine, Guizhou University, Guiyang, 550025, China. Electronic address: lzli@gzu.edu.cn., School of Medicine, Guizhou University, Guiyang, 550025, China. Electronic address: chenglv.78@163.com., School of Medicine, Guizhou University, Guiyang, 550025, China. Electronic address: huangui2022@gmail.com., School of Medicine, Guizhou University, Guiyang, 550025, China. Electronic address: 1635167177@qq.com., School of Preclinical Medicine of Zunyi Medical University, Zunyi, 563000, China. Electronic address: 550191498@qq.com., School of Medicine, Guizhou University, Guiyang, 550025, China. Electronic address: 1967400454@qq.com., NHC Key Laboratory of Pulmonary Immunological Diseases, Guizhou Provincial People 39;s Hospital, Guiyang, 550002, China; School of Medicine, Guizhou University, Guiyang, 550025, China. Electronic address: nienyj@hotmail.com.,
    1. Year: 2023
    2. Date: Feb 16
    3. Epub Date: 2023 02 16
  2. Journal: Biochemical and Biophysical Research Communications
    1. 653
    2. Pages: 106-114
  4. Type of Article: Article
  1. Abstract:

    Immunotherapy is the new approach for cancer treatment that can be achieved through several strategies, one of which is dendritic cells (DCs) vaccine therapy. However, traditional DC vaccination lacks accurate targeting, so DC vaccine preparation needs to be optimized. Immunosuppressive CD4+Foxp3+ regulatory T cells (Tregs) in the tumor microenvironment can promote tumor immune escape. Therefore, targeting Tregs has become a strategy for tumor immunotherapy. In this study, we found that HMGN1 (N1, a dendritic cell-activating TLR4 agonist) and 3M-052 (a newly synthesized TLR7/8 agonist) synergistically stimulate DCs maturation and increase the production of proinflammatory cytokines TNFa and IL-12. In a colon cancer mice model, vaccination with N1 and 3M-052 stimulated and tumor antigen-loaded DCs combined with anti-TNFR2 inhibited tumor growth in mice, and the antitumor effect was mainly achieved through stimulation of cytotoxic CD8 T cell activation and depletion of Tregs. Overall, the combinating of DC activation by N1 and 3M-052 with inhibition of Tregs by antagonizing TNFR2 as a therapeutic strategy may represent a more effective strategy for cancer treatment. Copyright © 2023 Elsevier Inc. All rights reserved.

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External Sources

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  2. DOI: 10.1016/j.bbrc.2023.02.039
  3. PMID: 36868074
  4. PII : S0006-291X(23)00213-9

Library Notes

  1. Fiscal Year: FY2022-2023
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