Tnfrsf9, also known as CD137 or 4-1BB, is a member of the tumor necrosis factor receptor superfamily. It functions as an activation marker for antigen-specific Tregs and is involved in regulating T-cell activation, proliferation, and differentiation. It can trigger signaling pathways such as the canonical NF-κB pathway, which is crucial for immune responses [1,3].

In non-small-cell lung cancer, the bimodal distribution of TNFRSF9 within tumor regulatory T cells was observed, and the gene signature of activated tumor Tregs including TNFRSF9 correlated with poor prognosis in lung adenocarcinoma [1].

In breast cancer, TNFRSF9 suppresses the progression of breast cancer via the p38MAPK/PAX6 signaling pathway. Knockdown of TNFRSF9 promotes breast cancer cell development, and it is found that TNFRSF9 regulates the phosphorylation of p38, thus affecting PAX6 expression [2].

In thyroid cancer, high TNFRSF9 expression correlated with worsened progression-free interval and the GBM Pathomics model based on pathohistological features could predict TNFRSF9 expression [4].

In conclusion, Tnfrsf9 plays a significant role in cancer-related immune regulation and tumor progression. Its study in various cancer models has provided insights into disease mechanisms, highlighting its potential as a target for immunotherapy in lung, breast, and thyroid cancers.