DHX34 deficiency triggers tumor-intrinsic immunity via a dsRNA-mediated type I interferon pathway activation in HCC
Tumors often evade immune surveillance by crippling their immunogenicity in the microenvironment. DHX34, an RNA helicase involved in nonsense-mediated mRNA decay pathway, is critical for aberrant RNA degradation. However, the effect of DHX34 in regulating the immunogenicity in hepatocellular carcino...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-09-01
|
| Series: | Neoplasia: An International Journal for Oncology Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558625000788 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | Tumors often evade immune surveillance by crippling their immunogenicity in the microenvironment. DHX34, an RNA helicase involved in nonsense-mediated mRNA decay pathway, is critical for aberrant RNA degradation. However, the effect of DHX34 in regulating the immunogenicity in hepatocellular carcinoma (HCC) is still unclear. Here, a surprising function of DHX34 in inhibited HCC immunogenicity is identified. DHX34-deficient tumors were infiltrated by activated T cells that impaired tumor growth and enhanced survival in mice. Mechanistically, DHX34 depletion triggered dsRNA accumulation which may activate cytosolic RNA-sensing pathway effectors such as MAVS, p-IKK, p-IRF3, and the subsequent type-I interferon response, evoking tumor-intrinsic immunity and leading to CD8 T activation. Collectively, DHX34 is implicated as a regulator that orchestrates a barrier in HCC by suppressing dsRNA-driven innate immune activation. Targeting DHX34 may enhance tumor immunogenicity and synergize with immunotherapies, offering a novel therapeutic strategy for HCC. |
|---|---|
| ISSN: | 1476-5586 |