Work

Exon-6 truncated p53 Suppresses Innate Immune Responses to Facilitate Immune Evasion in Bladder Cancer

Year: 2026

Type: article

Abstract: Previous studies have reported that truncated p53 exhibits pro-tumorigenic properties; however, whether it contributes to immune evasion by influencing the immune microenvironment remains unclear.Here, we report that exon-6-truncated p53 isoforms (E6-trunc p53) inhibit type I interferon (IFN-I) signaling, thereby supporting tumor cell survival and enabling immune evasion.Ectopic expression of E6-trunc p53 reduces T-cell infiltration into tumors and markedly promotes in vivo tumor growth in an immune-dependent manner.Mechanistically, E6-trunc p53 interacts with TBK1, thereby preventing cell-intrinsic activation of innate immune pathways and suppressing IFN-I-mediated antitumor immunity.Additionally, silencing E6-trunc p53 leads to robust upregulation of IFN-I signaling and induces tumor cell death.Deletion of TBK1 or IFN-β markedly rescues the cell death triggered by knockdown of E6-trunc p53.Notably, TP53 truncating mutations correlate inversely with the extent of T-cell infiltration and predict poor responsiveness to immunotherapy in patients with bladder cancer.Collectively, our findings reveal a novel oncogenic role of E6-trunc p53 in modulating IFN-I signaling and driving tumor malignancy and immune evasion.

Source: International Journal of Biological Sciences

DOI: 10.7150/ijbs.131491