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A TNFR2 antibody by countering immunosuppression cooperates with HMGN1 and R848 immune stimulants to inhibit murine colon cancer
Jiang, Mengmeng1; Liu, Jia2,3; Yang, De2; Tross, Debra2; Li, Ping1; Chen, Fengyang1; Alam, Md Masud2; Faustman, Denise L.4; Oppenheim, Joost J.2; Chen, Xin1,5,6,7
2021-12-01
Source PublicationInternational Immunopharmacology
ISSN1567-5769
Volume101
Abstract

Immunosuppressive CD4Foxp3 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.

KeywordAntitumor cd4+foxp3+ Regulatory t Cells (Tregs) Hmgn1 And R848 Immunotherapy Tnfr2
DOI10.1016/j.intimp.2021.108345
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaImmunology ; Pharmacology & Pharmacy
WOS SubjectImmunology ; Pharmacology & Pharmacy
WOS IDWOS:000721035400005
Scopus ID2-s2.0-85119116540
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Cited Times [WOS]:1   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Corresponding AuthorOppenheim, Joost J.; Chen, Xin
Affiliation1.Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, 999078, China
2.Laboratory of Cancer Immunometabolism, Center for Cancer Research, National Cancer Institute at Frederick, NIH, Frederick, United States
3.Department of Pharmacy, Changchun University of Chinese Medicine, Changchun, 130117, China
4.Immunobiology Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston, United States
5.Department of Pharmaceutical Science, Faculty of Health Sciences, University of Macau, 999078, China
6.MoE Frontiers Science Center for Precision Oncology, University of Macau, 999078, China
7.Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, 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
Jiang, Mengmeng,Liu, Jia,Yang, De,et al. A TNFR2 antibody by countering immunosuppression cooperates with HMGN1 and R848 immune stimulants to inhibit murine colon cancer[J]. International Immunopharmacology,2021,101.
APA Jiang, Mengmeng,Liu, Jia,Yang, De,Tross, Debra,Li, Ping,Chen, Fengyang,Alam, Md Masud,Faustman, Denise L.,Oppenheim, Joost J.,&Chen, Xin.(2021).A TNFR2 antibody by countering immunosuppression cooperates with HMGN1 and R848 immune stimulants to inhibit murine colon cancer.International Immunopharmacology,101.
MLA Jiang, Mengmeng,et al."A TNFR2 antibody by countering immunosuppression cooperates with HMGN1 and R848 immune stimulants to inhibit murine colon cancer".International Immunopharmacology 101(2021).
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