KDM3A Ablation Activates Endogenous Retrovirus Expression to Stimulate Antitumor Immunity in Gastric Cancer
Abstract: The success of immunotherapy for cancer treatment is limited by the presence of an immunosuppressive tumor microenvironment (TME); Therefore, identifying novel targets to that can reverse this immunosuppressive TME and enhance immunotherapy efficacy is essential. In this study, enrichment analysis based on publicly available single‐cell and bulk RNA sequencing data from gastric cancer patients are conducted, and found that tumor‐intrinsic interferon (IFN) plays a central role in TME regulation. The results shows that KDM3A over‐expression suppresses the tumor‐intrinsic IFN response and inhibits KDM3A, either genomically or pharmacologically, which effectively promotes IFN responses by activating endogenous retroviruses (ERVs). KDM3A ablation reconfigures the dsRNA‐MAVS‐IFN axis by modulating H3K4me2, enhancing the infiltration and function of CD8 T cells, and simultaneously reducing the presence of regulatory T cells, resulting in a reshaped TME in vivo. In addition, combining anti‐PD1 therapy with KDM3A inhibition effectively inhibited tumor growth. In conclusions, this study highlights KDM3A as a potential target for TME remodeling and the enhancement of antitumor immunity in gastric cancer through the regulation of the ERV‐MAVS‐IFN axis.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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KDM3A Ablation Activates Endogenous Retrovirus Expression to Stimulate Antitumor Immunity in Gastric Cancer ; day:19 ; month:07 ; year:2024 ; extent:17
Advanced science ; (19.07.2024) (gesamt 17)
- Creator
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Zheng, Jiabin
Feng, Huolun
Lin, Jiatong
Zhou, Jianlong
Xi, Zhihui
Zhang, Yucheng
Ling, Fa
Liu, Yongfeng
Wang, Junjiang
Hou, Tieying
Xing, Fan
Li, Yong
- DOI
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10.1002/advs.202309983
- URN
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urn:nbn:de:101:1-2407201412240.925585195918
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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14.08.2025, 11:00 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Zheng, Jiabin
- Feng, Huolun
- Lin, Jiatong
- Zhou, Jianlong
- Xi, Zhihui
- Zhang, Yucheng
- Ling, Fa
- Liu, Yongfeng
- Wang, Junjiang
- Hou, Tieying
- Xing, Fan
- Li, Yong
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