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

  • Biochem Biophys Res Commun. 2023 Apr 23:653:106-114. doi: 10.1016/j.bbrc.2023.02.039.
Lan Zhu  1 ,  Xiangyan Zhang  2 ,  Xin Chen  3 ,  De Yang  4 ,  Yujie Nie  5 ,  Runsang Pan  6 ,  Linzhao Li  7 ,  Chenglv Wang  8 ,  Huan Gui  9 ,  Shuanghui Chen  10 ,  Qianyu Jing  11 ,  Mengjiao Wang  12 ,  Yingjie Nie  13
Affiliations
  • 1. School of Medicine, Guizhou University, Guiyang, 550025, China. Electronic address: [email protected].
  • 2. NHC Key Laboratory of Pulmonary Immunological Diseases, Guizhou Provincial People's Hospital, Guiyang, 550002, China. Electronic address: [email protected].
  • 3. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR, 999078, China. Electronic address: [email protected].
  • 4. Laboratory of Cancer Immunometabolism, Center for Cancer Research, National Cancer Institute at Frederick, NIH, Frederick, MD, USA. Electronic address: [email protected].
  • 5. NHC Key Laboratory of Pulmonary Immunological Diseases, Guizhou Provincial People's Hospital, Guiyang, 550002, China. Electronic address: [email protected].
  • 6. Department of Pathophysiology, School of Basic Medicine, Guizhou Medical University, Guiyang, 550025, China. Electronic address: [email protected].
  • 7. School of Medicine, Guizhou University, Guiyang, 550025, China. Electronic address: [email protected].
  • 8. School of Medicine, Guizhou University, Guiyang, 550025, China. Electronic address: [email protected].
  • 9. School of Medicine, Guizhou University, Guiyang, 550025, China. Electronic address: [email protected].
  • 10. School of Medicine, Guizhou University, Guiyang, 550025, China. Electronic address: [email protected].
  • 11. School of Preclinical Medicine of Zunyi Medical University, Zunyi, 563000, China. Electronic address: [email protected].
  • 12. School of Medicine, Guizhou University, Guiyang, 550025, China. Electronic address: [email protected].
  • 13. NHC Key Laboratory of Pulmonary Immunological Diseases, Guizhou Provincial People's Hospital, Guiyang, 550002, China; School of Medicine, Guizhou University, Guiyang, 550025, China. Electronic address: [email protected].
PMID: 36868074 DOI: 10.1016/j.bbrc.2023.02.039
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 TNFα 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.

Keywords
Anti-TNFR2; Antitumor; CD4(+)Foxp3(+)regulatory T cells (Tregs); Dendritic cells (DCs); HMGN1 and 3M-052; Immunotherapy.
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