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

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. • HMGN1 and 3M-052 synergistically induce DC maturation and promote its ability to produce TNF-α and IL-12. • HMGN1 and 3M-052 stimulated DCs vaccines combined with anti-TNFR2 effectively inhibits the growth of murine colon cancer. • The combination of HMGN1 and 3M-052 stimulated DCs vaccines with anti-TNFR2 activated the antitumor immune response. • HMGN1 and 3M-052 May have potential as adjuvants for DC-based immunotherapy. • TNFR2 can be used as a new target for tumor immunotherapy. [ABSTRACT FROM AUTHOR]