Ubiquitination of CD47 Regulates Innate Anti‐Tumor Immune Response
Abstract In addition to adaptive immune checkpoint of PD‐1/PD‐L1, the innate immune checkpoint SIRPα/CD47 plays an important role in regulation of tumor immune escape. However, the mechanism of CD47 ubiquitination on tumor immune escape remains unclear. Here it is found that TRAF2 bound to the C‐ter...
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| Format: | Article |
| Language: | English |
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Wiley
2025-02-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202412205 |
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| author | Qian Gou Bingjun Yan Yalan Duan Yilei Guo Jing Qian Juanjuan Shi Yongzhong Hou |
| author_facet | Qian Gou Bingjun Yan Yalan Duan Yilei Guo Jing Qian Juanjuan Shi Yongzhong Hou |
| author_sort | Qian Gou |
| collection | DOAJ |
| description | Abstract In addition to adaptive immune checkpoint of PD‐1/PD‐L1, the innate immune checkpoint SIRPα/CD47 plays an important role in regulation of tumor immune escape. However, the mechanism of CD47 ubiquitination on tumor immune escape remains unclear. Here it is found that TRAF2 bound to the C‐terminal of CD47 cytoplasmic fragment and induced its ubiquitination, leading to inhibition of CD47 autophagic degradation by disrupting its binding to LC3, which in turn inhibited macrophage phagocytosis and promoted tumor immune escape. In contrast, loss of TRAF2 facilitated CD47 autophagic degradation and inhibited tumor immune escape. Moreover, autophagy induction promoted CD47 degradation and enhanced the efficacy of CD47 antibody anti‐tumor immunotherapy. These findings revealed a novel mechanism of ubiquitination of CD47 on tumor immune escape. |
| format | Article |
| id | doaj-art-64dd73f4745f4ab092968b43c14d3575 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-64dd73f4745f4ab092968b43c14d35752025-02-04T13:14:54ZengWileyAdvanced Science2198-38442025-02-01125n/an/a10.1002/advs.202412205Ubiquitination of CD47 Regulates Innate Anti‐Tumor Immune ResponseQian Gou0Bingjun Yan1Yalan Duan2Yilei Guo3Jing Qian4Juanjuan Shi5Yongzhong Hou6School of Life Science Jiangsu University Zhenjiang Jiangsu Province 212013 People's Republic of ChinaSchool of Life Science Jiangsu University Zhenjiang Jiangsu Province 212013 People's Republic of ChinaSchool of Life Science Jiangsu University Zhenjiang Jiangsu Province 212013 People's Republic of ChinaSchool of Life Science Jiangsu University Zhenjiang Jiangsu Province 212013 People's Republic of ChinaSchool of Life Science Jiangsu University Zhenjiang Jiangsu Province 212013 People's Republic of ChinaSchool of Life Science Jiangsu University Zhenjiang Jiangsu Province 212013 People's Republic of ChinaSchool of Life Science Jiangsu University Zhenjiang Jiangsu Province 212013 People's Republic of ChinaAbstract In addition to adaptive immune checkpoint of PD‐1/PD‐L1, the innate immune checkpoint SIRPα/CD47 plays an important role in regulation of tumor immune escape. However, the mechanism of CD47 ubiquitination on tumor immune escape remains unclear. Here it is found that TRAF2 bound to the C‐terminal of CD47 cytoplasmic fragment and induced its ubiquitination, leading to inhibition of CD47 autophagic degradation by disrupting its binding to LC3, which in turn inhibited macrophage phagocytosis and promoted tumor immune escape. In contrast, loss of TRAF2 facilitated CD47 autophagic degradation and inhibited tumor immune escape. Moreover, autophagy induction promoted CD47 degradation and enhanced the efficacy of CD47 antibody anti‐tumor immunotherapy. These findings revealed a novel mechanism of ubiquitination of CD47 on tumor immune escape.https://doi.org/10.1002/advs.202412205autophagyCD47immune escapeTRAF2ubiquitination |
| spellingShingle | Qian Gou Bingjun Yan Yalan Duan Yilei Guo Jing Qian Juanjuan Shi Yongzhong Hou Ubiquitination of CD47 Regulates Innate Anti‐Tumor Immune Response Advanced Science autophagy CD47 immune escape TRAF2 ubiquitination |
| title | Ubiquitination of CD47 Regulates Innate Anti‐Tumor Immune Response |
| title_full | Ubiquitination of CD47 Regulates Innate Anti‐Tumor Immune Response |
| title_fullStr | Ubiquitination of CD47 Regulates Innate Anti‐Tumor Immune Response |
| title_full_unstemmed | Ubiquitination of CD47 Regulates Innate Anti‐Tumor Immune Response |
| title_short | Ubiquitination of CD47 Regulates Innate Anti‐Tumor Immune Response |
| title_sort | ubiquitination of cd47 regulates innate anti tumor immune response |
| topic | autophagy CD47 immune escape TRAF2 ubiquitination |
| url | https://doi.org/10.1002/advs.202412205 |
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