Exon-6 truncated p53 Suppresses Innate Immune Responses to Facilitate Immune Evasion in Bladder Cancer.
5 affiliations
- 1Senior Department of Urology, Chinese PLA General Hospital, Beijing, China.
- 2School of medicine, Nankai University, Tianjin, 300071, China.
- 3Department of Urology Laboratory, Chinese PLA General Hospital, Beijing, China.
- 4Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China.
- 5Medical School of PLA, Beijing, China.
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.
Related
- Non-canonical function of SCIMP restricts JAK1 activity to counteract immune evasion in bladder cancer
- Integrative single-cell and computational pathology analyses reveal a C11orf24-associated stem-like epithelial population linked to tumor microenvironment remodeling and immune evasion in bladder cancer
- Targeting NCAPG with Arundanine Suppresses Neutrophil/NET-Mediated Immune Evasion and Enhances CD8⁺ T Cell Function in Lung Squamous Cell Carcinoma.
- Overexpression of TUBA1A suppresses bladder cancer progression with potential modulation of autophagic activity and macrophage polarization
- HADHA K406 Lactylation Regulates Metabolic Reprogramming and Suppresses Immune Responses in Gastric Cancer.
BibTeX
@article{zhang2026exon6,
title = {{Exon-6 truncated p53 Suppresses Innate Immune Responses to Facilitate Immune Evasion in Bladder Cancer.}},
author = {Chi Zhang and Wenjie Wei and Senming Cao and Zhi Li and Chuang Wang and Wen Tao and Yuhao Dong and Chunyu Liu and Shun Wu and Shuo Tian and Qingbo Huang and Baojun Wang and Hongzhao Li and Xin Ma and Xu Zhang and Yan Huang},
journal = {International journal of biological sciences},
year = {2026},
month = sep,
doi = {10.7150/ijbs.131491},
url = {https://europepmc.org/article/MED/42909883},
note = {CC BY},
}
RIS
TY - JOUR
TI - Exon-6 truncated p53 Suppresses Innate Immune Responses to Facilitate Immune Evasion in Bladder Cancer.
AU - Chi Zhang
AU - Wenjie Wei
AU - Senming Cao
AU - Zhi Li
AU - Chuang Wang
AU - Wen Tao
AU - Yuhao Dong
AU - Chunyu Liu
AU - Shun Wu
AU - Shuo Tian
AU - Qingbo Huang
AU - Baojun Wang
AU - Hongzhao Li
AU - Xin Ma
AU - Xu Zhang
AU - Yan Huang
PY - 2026
DA - 2026/09/11
JO - International journal of biological sciences
DO - 10.7150/ijbs.131491
UR - https://europepmc.org/article/MED/42909883
AB - 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.
SN - 1449-2288
ER -