Targeting WEE1 in tumor-associated dendritic cells potentiates antitumor immunity via the cGAS/STING pathway
Summary: DNA damage profoundly affects cancer progression and immune cell function. While research primarily focuses on tumor cells, the effects of DNA damage on immune cells remain understudied. Here, we observe significant DNA damage in tumor-associated dendritic cells (TADCs), accompanied by the...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-06-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725005042 |
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| author | Ian-Ian Ng Zhihua Zhang Kaimin Xiao Minjie Ye Tingzhong Tian Yaoji Zhu Yuan He Ling Chu Haidong Tang |
| author_facet | Ian-Ian Ng Zhihua Zhang Kaimin Xiao Minjie Ye Tingzhong Tian Yaoji Zhu Yuan He Ling Chu Haidong Tang |
| author_sort | Ian-Ian Ng |
| collection | DOAJ |
| description | Summary: DNA damage profoundly affects cancer progression and immune cell function. While research primarily focuses on tumor cells, the effects of DNA damage on immune cells remain understudied. Here, we observe significant DNA damage in tumor-associated dendritic cells (TADCs), accompanied by the upregulation of the serine/threonine kinase WEE1, a crucial regulator of DNA damage repair. Interestingly, DNA damage also stimulates DC activation. WEE1 inhibition activates TADCs through the cGAS/STING pathway, increasing IL-12 and type I interferon expression, thus enhancing the antitumor immune response and improving tumor control. Additionally, WEE1 inhibition augments the efficacy of DC vaccines and synergizes with immune checkpoint blockade therapy. These findings highlight a pivotal role of WEE1 signaling in DNA damage repair in DCs within the tumor microenvironment, which in turn suppresses the antitumor immune response. Therefore, targeting WEE1 in DCs represents a promising approach to enhance T cell activation and improve the effectiveness of cancer immunotherapy. |
| format | Article |
| id | doaj-art-bfb21e1c009b429a8d19518eae8e3f14 |
| institution | DOAJ |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-bfb21e1c009b429a8d19518eae8e3f142025-08-20T03:13:03ZengElsevierCell Reports2211-12472025-06-0144611573310.1016/j.celrep.2025.115733Targeting WEE1 in tumor-associated dendritic cells potentiates antitumor immunity via the cGAS/STING pathwayIan-Ian Ng0Zhihua Zhang1Kaimin Xiao2Minjie Ye3Tingzhong Tian4Yaoji Zhu5Yuan He6Ling Chu7Haidong Tang8State Key Laboratory of Molecular Oncology, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, ChinaState Key Laboratory of Molecular Oncology, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China; College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, ChinaState Key Laboratory of Molecular Oncology, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China; Joint Graduate Program of Peking-Tsinghua-NIBS, School of Life Sciences, Tsinghua University, Beijing 100084, ChinaState Key Laboratory of Molecular Oncology, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, ChinaInstitute for Interdisciplinary Information Sciences, Tsinghua University, Beijing 100084, ChinaState Key Laboratory of Molecular Oncology, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, ChinaResearch Beyond Borders, Boehringer Ingelheim, Shanghai 200120, ChinaState Key Laboratory of Molecular Oncology, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, ChinaState Key Laboratory of Molecular Oncology, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China; Corresponding authorSummary: DNA damage profoundly affects cancer progression and immune cell function. While research primarily focuses on tumor cells, the effects of DNA damage on immune cells remain understudied. Here, we observe significant DNA damage in tumor-associated dendritic cells (TADCs), accompanied by the upregulation of the serine/threonine kinase WEE1, a crucial regulator of DNA damage repair. Interestingly, DNA damage also stimulates DC activation. WEE1 inhibition activates TADCs through the cGAS/STING pathway, increasing IL-12 and type I interferon expression, thus enhancing the antitumor immune response and improving tumor control. Additionally, WEE1 inhibition augments the efficacy of DC vaccines and synergizes with immune checkpoint blockade therapy. These findings highlight a pivotal role of WEE1 signaling in DNA damage repair in DCs within the tumor microenvironment, which in turn suppresses the antitumor immune response. Therefore, targeting WEE1 in DCs represents a promising approach to enhance T cell activation and improve the effectiveness of cancer immunotherapy.http://www.sciencedirect.com/science/article/pii/S2211124725005042CP: CancerCP: Immunology |
| spellingShingle | Ian-Ian Ng Zhihua Zhang Kaimin Xiao Minjie Ye Tingzhong Tian Yaoji Zhu Yuan He Ling Chu Haidong Tang Targeting WEE1 in tumor-associated dendritic cells potentiates antitumor immunity via the cGAS/STING pathway Cell Reports CP: Cancer CP: Immunology |
| title | Targeting WEE1 in tumor-associated dendritic cells potentiates antitumor immunity via the cGAS/STING pathway |
| title_full | Targeting WEE1 in tumor-associated dendritic cells potentiates antitumor immunity via the cGAS/STING pathway |
| title_fullStr | Targeting WEE1 in tumor-associated dendritic cells potentiates antitumor immunity via the cGAS/STING pathway |
| title_full_unstemmed | Targeting WEE1 in tumor-associated dendritic cells potentiates antitumor immunity via the cGAS/STING pathway |
| title_short | Targeting WEE1 in tumor-associated dendritic cells potentiates antitumor immunity via the cGAS/STING pathway |
| title_sort | targeting wee1 in tumor associated dendritic cells potentiates antitumor immunity via the cgas sting pathway |
| topic | CP: Cancer CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725005042 |
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