Arf1 Ablation in Colorectal Cancer Cells Activates a Super Signal Complex in DC to Enhance Anti‐Tumor Immunity
Abstract The anti‐tumor immune response relies on interactions among tumor cells and immune cells. However, the molecular mechanisms by which tumor cells regulate DCs as well as DCs regulate T cells remain enigmatic. Here, the authors identify a super signaling complex in DCs that mediates the Arf1‐...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-11-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202305089 |
| _version_ | 1797627764083261440 |
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| author | Handong Ma Wanqi Fang Qiaoming Li Yuetong Wang Steven X. Hou |
| author_facet | Handong Ma Wanqi Fang Qiaoming Li Yuetong Wang Steven X. Hou |
| author_sort | Handong Ma |
| collection | DOAJ |
| description | Abstract The anti‐tumor immune response relies on interactions among tumor cells and immune cells. However, the molecular mechanisms by which tumor cells regulate DCs as well as DCs regulate T cells remain enigmatic. Here, the authors identify a super signaling complex in DCs that mediates the Arf1‐ablation‐induced anti‐tumor immunity. They find that the Arf1‐ablated tumor cells release OxLDL, HMGB1, and genomic DNA, which together bound to a coreceptor complex of CD36/TLR2/TLR6 on DC surface. The complex then is internalized into the Rab7‐marked endosome in DCs, and further joined by components of the NF‐κB, NLRP3 inflammasome and cGAS‐STING triple pathways to form a super signal complex for producing different cytokines, which together promote CD8+ T cell tumor infiltration, cross‐priming and stemness. Blockage of the HMGB1‐gDNA complex or reducing expression in each member of the coreceptors or the cGAS/STING pathway prevents production of the cytokines. Moreover, depletion of the type I IFNs and IL‐1β cytokines abrogate tumor regression in mice bearing the Arf1‐ablated tumor cells. These findings reveal a new molecular mechanism by which dying tumor cells releasing several factors to activate the triple pathways in DC for producing multiple cytokines to simultaneously promote DC activation, T cell infiltration, cross‐priming and stemness. |
| first_indexed | 2024-03-11T10:29:04Z |
| format | Article |
| id | doaj.art-c953d2d18844485a9aa4a7eef0902b49 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-11T10:29:04Z |
| publishDate | 2023-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-c953d2d18844485a9aa4a7eef0902b492023-11-15T05:46:36ZengWileyAdvanced Science2198-38442023-11-011032n/an/a10.1002/advs.202305089Arf1 Ablation in Colorectal Cancer Cells Activates a Super Signal Complex in DC to Enhance Anti‐Tumor ImmunityHandong Ma0Wanqi Fang1Qiaoming Li2Yuetong Wang3Steven X. Hou4Department of Cell and Developmental Biology at School of Life Sciences State Key Laboratory of Genetic Engineering Institute of Metabolism and Integrative Biology Human Phenome Institute Department of Liver Surgery and Transplantation of Liver Cancer Institute at Zhongshan Hospital Fudan University Shanghai 200438 ChinaDepartment of Cell and Developmental Biology at School of Life Sciences State Key Laboratory of Genetic Engineering Institute of Metabolism and Integrative Biology Human Phenome Institute Department of Liver Surgery and Transplantation of Liver Cancer Institute at Zhongshan Hospital Fudan University Shanghai 200438 ChinaDepartment of Cell and Developmental Biology at School of Life Sciences State Key Laboratory of Genetic Engineering Institute of Metabolism and Integrative Biology Human Phenome Institute Department of Liver Surgery and Transplantation of Liver Cancer Institute at Zhongshan Hospital Fudan University Shanghai 200438 ChinaDepartment of Cell and Developmental Biology at School of Life Sciences State Key Laboratory of Genetic Engineering Institute of Metabolism and Integrative Biology Human Phenome Institute Department of Liver Surgery and Transplantation of Liver Cancer Institute at Zhongshan Hospital Fudan University Shanghai 200438 ChinaDepartment of Cell and Developmental Biology at School of Life Sciences State Key Laboratory of Genetic Engineering Institute of Metabolism and Integrative Biology Human Phenome Institute Department of Liver Surgery and Transplantation of Liver Cancer Institute at Zhongshan Hospital Fudan University Shanghai 200438 ChinaAbstract The anti‐tumor immune response relies on interactions among tumor cells and immune cells. However, the molecular mechanisms by which tumor cells regulate DCs as well as DCs regulate T cells remain enigmatic. Here, the authors identify a super signaling complex in DCs that mediates the Arf1‐ablation‐induced anti‐tumor immunity. They find that the Arf1‐ablated tumor cells release OxLDL, HMGB1, and genomic DNA, which together bound to a coreceptor complex of CD36/TLR2/TLR6 on DC surface. The complex then is internalized into the Rab7‐marked endosome in DCs, and further joined by components of the NF‐κB, NLRP3 inflammasome and cGAS‐STING triple pathways to form a super signal complex for producing different cytokines, which together promote CD8+ T cell tumor infiltration, cross‐priming and stemness. Blockage of the HMGB1‐gDNA complex or reducing expression in each member of the coreceptors or the cGAS/STING pathway prevents production of the cytokines. Moreover, depletion of the type I IFNs and IL‐1β cytokines abrogate tumor regression in mice bearing the Arf1‐ablated tumor cells. These findings reveal a new molecular mechanism by which dying tumor cells releasing several factors to activate the triple pathways in DC for producing multiple cytokines to simultaneously promote DC activation, T cell infiltration, cross‐priming and stemness.https://doi.org/10.1002/advs.202305089anti‐tumor immunityT cell infiltrationNLRP3cGAS‐STINGoxLDL |
| spellingShingle | Handong Ma Wanqi Fang Qiaoming Li Yuetong Wang Steven X. Hou Arf1 Ablation in Colorectal Cancer Cells Activates a Super Signal Complex in DC to Enhance Anti‐Tumor Immunity Advanced Science anti‐tumor immunity T cell infiltration NLRP3 cGAS‐STING oxLDL |
| title | Arf1 Ablation in Colorectal Cancer Cells Activates a Super Signal Complex in DC to Enhance Anti‐Tumor Immunity |
| title_full | Arf1 Ablation in Colorectal Cancer Cells Activates a Super Signal Complex in DC to Enhance Anti‐Tumor Immunity |
| title_fullStr | Arf1 Ablation in Colorectal Cancer Cells Activates a Super Signal Complex in DC to Enhance Anti‐Tumor Immunity |
| title_full_unstemmed | Arf1 Ablation in Colorectal Cancer Cells Activates a Super Signal Complex in DC to Enhance Anti‐Tumor Immunity |
| title_short | Arf1 Ablation in Colorectal Cancer Cells Activates a Super Signal Complex in DC to Enhance Anti‐Tumor Immunity |
| title_sort | arf1 ablation in colorectal cancer cells activates a super signal complex in dc to enhance anti tumor immunity |
| topic | anti‐tumor immunity T cell infiltration NLRP3 cGAS‐STING oxLDL |
| url | https://doi.org/10.1002/advs.202305089 |
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