TNFR2

Class

Anti-TNFR2 monoclonal antibody

Pathway

Immuno-oncology; TNFR2 blockade to reduce Treg-mediated immunosuppression

Notes

original target text: TNFR2 (tumor necrosis factor receptor 2) | original target text: TNFR2 (inhibitor)

Tumor necrosis factor receptor 2 (TNFR2) is a cell-surface receptor for the cytokine TNF, expressed selectively on certain immune cell subsets, most notably regulatory T cells (Tregs), as well as some endothelial and tumor cells. Unlike its more widely expressed sibling TNFR1, TNFR2 signaling tends to promote survival and expansion of Tregs, the immune cells that dampen anti-tumor immune responses and maintain tolerance. In many solid tumors, TNFR2-high Tregs accumulate within the tumor microenvironment and suppress cytotoxic T-cell activity, allowing cancer cells to evade immune attack. Antibodies designed to block or deplete TNFR2 aim to reduce this suppressive population, thereby unleashing a stronger anti-tumor immune response, a strategy that fits within the broader field of immuno-oncology alongside checkpoint inhibitors. Because TNFR2 expression is relatively restricted compared to TNFR1, targeting it is intended to achieve more selective effects on tumor-infiltrating Tregs while sparing normal tissues that rely on TNFR1-mediated inflammatory signaling. This mechanism is being explored primarily in cancers where Treg-driven immunosuppression is thought to limit the efficacy of existing immunotherapies. The overall rationale is to combine reduction of immune suppression with potential direct effects on TNFR2-expressing tumor cells in certain cancer types.