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!
|
| _version_ | 1849729394313003008 |
|---|---|
| author | Chunli Zhang Limin Huang Zeyu Li Qian Wang Nanbin Liu Chongyu Zhang Xi Liu Chen Zhang Gaixia He Jin Sun Zongfang Li Hongwei Tian |
| author_facet | Chunli Zhang Limin Huang Zeyu Li Qian Wang Nanbin Liu Chongyu Zhang Xi Liu Chen Zhang Gaixia He Jin Sun Zongfang Li Hongwei Tian |
| author_sort | Chunli Zhang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-53e95024d6c841f497e8ef930136ef2e |
| institution | DOAJ |
| issn | 1476-5586 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj-art-53e95024d6c841f497e8ef930136ef2e2025-08-20T03:09:14ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862025-09-016710119810.1016/j.neo.2025.101198DHX34 deficiency triggers tumor-intrinsic immunity via a dsRNA-mediated type I interferon pathway activation in HCCChunli Zhang0Limin Huang1Zeyu Li2Qian Wang3Nanbin Liu4Chongyu Zhang5Xi Liu6Chen Zhang7Gaixia He8Jin Sun9Zongfang Li10Hongwei Tian11Department of General Surgery, National-Local Joint Engineering Research Center of Biodiagnostic & Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, PR ChinaDepartment of General Surgery, National-Local Joint Engineering Research Center of Biodiagnostic & Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, PR ChinaDepartment of General Surgery, National-Local Joint Engineering Research Center of Biodiagnostic & Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, PR ChinaDepartment of Tumor and Immunology in Precision Medical Institute, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, PR ChinaDepartment of General Surgery, National-Local Joint Engineering Research Center of Biodiagnostic & Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, PR ChinaDepartment of General Surgery, National-Local Joint Engineering Research Center of Biodiagnostic & Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, PR ChinaDepartment of General Surgery, National-Local Joint Engineering Research Center of Biodiagnostic & Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, PR ChinaDepartment of General Surgery, National-Local Joint Engineering Research Center of Biodiagnostic & Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, PR ChinaDepartment of General Surgery, National-Local Joint Engineering Research Center of Biodiagnostic & Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, PR China; Shaanxi Provincial Clinical Medical Research Center for Liver and Spleen Diseases, CHESS-Shaanxi consortium, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, PR ChinaDepartment of General Surgery, National-Local Joint Engineering Research Center of Biodiagnostic & Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, PR China; Department of Tumor and Immunology in Precision Medical Institute, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, PR ChinaDepartment of General Surgery, National-Local Joint Engineering Research Center of Biodiagnostic & Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, PR China; Department of Tumor and Immunology in Precision Medical Institute, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China; Shaanxi Provincial Clinical Medical Research Center for Liver and Spleen Diseases, CHESS-Shaanxi consortium, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, PR China; Key Laboratory of Environment and Genes Related to Diseases, Xi’an Jiaotong University, Ministry of Education of China, Shaanxi, PR China; Corresponding authors at: National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi’an Jiaotong University, 71004 Xi’an, PR China.Department of General Surgery, National-Local Joint Engineering Research Center of Biodiagnostic & Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, PR China; Department of Tumor and Immunology in Precision Medical Institute, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China; Corresponding authors at: National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi’an Jiaotong University, 71004 Xi’an, PR China.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.http://www.sciencedirect.com/science/article/pii/S1476558625000788DHX34Hepatocellular carcinomadsRNAImmune evasionType I interferon |
| spellingShingle | Chunli Zhang Limin Huang Zeyu Li Qian Wang Nanbin Liu Chongyu Zhang Xi Liu Chen Zhang Gaixia He Jin Sun Zongfang Li Hongwei Tian DHX34 deficiency triggers tumor-intrinsic immunity via a dsRNA-mediated type I interferon pathway activation in HCC Neoplasia: An International Journal for Oncology Research DHX34 Hepatocellular carcinoma dsRNA Immune evasion Type I interferon |
| title | DHX34 deficiency triggers tumor-intrinsic immunity via a dsRNA-mediated type I interferon pathway activation in HCC |
| title_full | DHX34 deficiency triggers tumor-intrinsic immunity via a dsRNA-mediated type I interferon pathway activation in HCC |
| title_fullStr | DHX34 deficiency triggers tumor-intrinsic immunity via a dsRNA-mediated type I interferon pathway activation in HCC |
| title_full_unstemmed | DHX34 deficiency triggers tumor-intrinsic immunity via a dsRNA-mediated type I interferon pathway activation in HCC |
| title_short | DHX34 deficiency triggers tumor-intrinsic immunity via a dsRNA-mediated type I interferon pathway activation in HCC |
| title_sort | dhx34 deficiency triggers tumor intrinsic immunity via a dsrna mediated type i interferon pathway activation in hcc |
| topic | DHX34 Hepatocellular carcinoma dsRNA Immune evasion Type I interferon |
| url | http://www.sciencedirect.com/science/article/pii/S1476558625000788 |
| work_keys_str_mv | AT chunlizhang dhx34deficiencytriggerstumorintrinsicimmunityviaadsrnamediatedtypeiinterferonpathwayactivationinhcc AT liminhuang dhx34deficiencytriggerstumorintrinsicimmunityviaadsrnamediatedtypeiinterferonpathwayactivationinhcc AT zeyuli dhx34deficiencytriggerstumorintrinsicimmunityviaadsrnamediatedtypeiinterferonpathwayactivationinhcc AT qianwang dhx34deficiencytriggerstumorintrinsicimmunityviaadsrnamediatedtypeiinterferonpathwayactivationinhcc AT nanbinliu dhx34deficiencytriggerstumorintrinsicimmunityviaadsrnamediatedtypeiinterferonpathwayactivationinhcc AT chongyuzhang dhx34deficiencytriggerstumorintrinsicimmunityviaadsrnamediatedtypeiinterferonpathwayactivationinhcc AT xiliu dhx34deficiencytriggerstumorintrinsicimmunityviaadsrnamediatedtypeiinterferonpathwayactivationinhcc AT chenzhang dhx34deficiencytriggerstumorintrinsicimmunityviaadsrnamediatedtypeiinterferonpathwayactivationinhcc AT gaixiahe dhx34deficiencytriggerstumorintrinsicimmunityviaadsrnamediatedtypeiinterferonpathwayactivationinhcc AT jinsun dhx34deficiencytriggerstumorintrinsicimmunityviaadsrnamediatedtypeiinterferonpathwayactivationinhcc AT zongfangli dhx34deficiencytriggerstumorintrinsicimmunityviaadsrnamediatedtypeiinterferonpathwayactivationinhcc AT hongweitian dhx34deficiencytriggerstumorintrinsicimmunityviaadsrnamediatedtypeiinterferonpathwayactivationinhcc |