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A TNFR2 antibody by countering immunosuppression cooperates with HMGN1 and R848 immune stimulants to inhibit murine colon cancer

  1. Author:
    Jiang, Mengmeng
    Liu,Jia
    Yang,De
    Tross,Debra
    Li, Ping
    Chen, Fengyang
    Alam,Md Masud
    Faustman, Denise L
    Oppenheim,Joost
    Chen, Xin

  2. Author Address

    Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macau SAR 999078, China., Laboratory of Cancer Immunometabolism, Center for Cancer Research, National Cancer Institute at Frederick, NIH, Frederick, MD, USA; Department of Pharmacy, Changchun University of Chinese Medicine, Changchun, Jilin 130117, China., Laboratory of Cancer Immunometabolism, Center for Cancer Research, National Cancer Institute at Frederick, NIH, Frederick, MD, USA., Immunobiology Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Laboratory of Cancer Immunometabolism, Center for Cancer Research, National Cancer Institute at Frederick, NIH, Frederick, MD, USA. Electronic address: Oppenhej@mail.nih.gov., Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macau SAR 999078, China; Department of Pharmaceutical Science, Faculty of Health Sciences, University of Macau, Macau SAR 999078, China; MoE Frontiers Science Center for Precision Oncology, University of Macau, Macau SAR 999078, China; Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, China. Electronic address: xchen@umac.mo.,
    1. Year: 2021
    2. Date: Nov 15
    3. Epub Date: 2021 11 15
  2. Journal: International immunopharmacology
    1. 101
    2. Pt A
    3. Pages: 108345
  4. Type of Article: Article
  5. Article Number: 108345
  6. ISSN: 1567-5769
  1. Abstract:

    Immunosuppressive CD4+Foxp3+ regulatory T cells (Tregs) promote tumor immune evasion and thus targeting of Tregs has become an strategy in cancer immunotherapy. Tumor necrosis factor receptor 2 (TNFR2) is highly expressed and important for the immunosuppressive function of Tregs in humans and mice. Thus, the benefit of targeting TNFR2 in cancer immunotherapy merits more investigation. A previous report identified a new murine monoclonal anti-TNFR2 antibody (designated TY101), which showed therapeutic efficacy in murine cancer models, but its mechanism of action was less understood. In this study, the capacity of a combination of immunostimulants to enhance the effect of this inhibitor of Tregs was investigated. We examined the efficacy of TY101 as an anti-tumor immune reagent combined with HMGN1 (N1, a dendritic cell activating TLR4 agonist) and R848 (a synthetic TLR7/8 agonist). This immunotherapeutic combination exerted synergistic antitumor effects as compared with any single treatment. The antitumor response was mainly mediated by the depletion of Tregs and stimulation of cytotoxic CD8 T cell activation. The result also suggested that the effect of TY101 was similar to that of anti-PD-L1 when used in combination with these immunostimulants. Therefore, we propose that treatment strategies of antagonizing TNFR2 on Tregs would behave as potent checkpoint inhibitors and can potentially be utilized to develop a novel antitumor immunotherapy. Copyright © 2021 Elsevier B.V. All rights reserved.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.intimp.2021.108345
  3. PMID: 34794079
  4. View record in Web of Science®
  5. WOS: 000721035400005
  6. PII : S1567-5769(21)00981-4

Library Notes

  1. Fiscal Year: FY2021-2022
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