Work

TNFR2 antagonsitic antibody induces the death of tumor infiltrating CD4+Foxp3+ regulatory T cells

Year: 2022

Type: preprint

Abstract: Background TNFR2 expression is a characteristic of highly potent immunosuppressive tumor infiltrating CD4 + Foxp3 + regulatory T cells (Tregs). There is now compelling evidence that TNF through TNFR2 preferentially stimulates the activation and expansion of Tregs. We and others, therefore, proposed that targeting of TNFR2 may provide a novel strategy in cancer immunotherapy. Several studies have showed the anti-tumor effect of TNFR2 antagonistic antibody in different tumor model. However, the exact action of TNFR2 antibody on Tregs remained fully understood. Method TY101, an anti-murine TNFR2 antibody, was used for exmining the effect of TNFR2 blockade on Treg proliferation and viability in vitro. The role of TNFR2 on Treg viability were further validated by TNFR2 konckout mice and in TY101-treated mouse tumor model. Results In this study, we found that TY101, an anti-mouse TNFR2 antibody, could inhibit TNF-induced proliferative expansion of Treg, indicative of an antagonistic property. To examine the effect of TY101 on Treg viability, we treated purified Tregs with dexamethasone (Dex) which was known to induce T cell death. The result showed that TY101 treatment furhter promoted Treg death in the presence of Dex. This led us to found that TNFR2 expression was crucial for the survival of Tregs. In mouse EG7 lymphoma model, treatment with TY101 potently inhibited tumor growth, resulting in a complete regression of tumor in 60% mice. The treatment with TY101 elicited potent antitumor immune responses in this model, accompanied by enhanced death of Treg cells. Conclusion This study therefore provides clear experimental evidence that the anti-tumor effect of TNFR2 antagonistic antibody can promote the death of Tregs, and this effect may be attributrable to the anti-tumor effect of TNFR2 antagonistic antibody.

Source: Research Square

DOI: 10.21203/rs.3.rs-1638143/v1