Inhibition of CK2/ING4 Pathway Facilitates Non‐Small Cell Lung Cancer Immunotherapy
Abstract Immune cells can protect against tumor progression by killing cancer cells, while aberrant expression of the immune checkpoint protein PD‐L1 (programmed death ligand 1) in cancer cells facilitates tumor immune escape and inhibits anti‐tumor immunotherapy. As a serine/threonine kinase, CK2 (...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-12-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202304068 |
| _version_ | 1797401800666513408 |
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| author | Qian Gou Huiqing Chen Mingjun Chen Juanjuan Shi Jianhua Jin Qian Liu Yongzhong Hou |
| author_facet | Qian Gou Huiqing Chen Mingjun Chen Juanjuan Shi Jianhua Jin Qian Liu Yongzhong Hou |
| author_sort | Qian Gou |
| collection | DOAJ |
| description | Abstract Immune cells can protect against tumor progression by killing cancer cells, while aberrant expression of the immune checkpoint protein PD‐L1 (programmed death ligand 1) in cancer cells facilitates tumor immune escape and inhibits anti‐tumor immunotherapy. As a serine/threonine kinase, CK2 (casein kinase 2) regulates tumor progression by multiple pathways, while it is still unclear the effect of CK2 on tumor immune escape. Here it is found that ING4 induced PD‐L1 autophagic degradation and inhibites non‐small cell lung cancer (NSCLC) immune escape by increasing T cell activity. However, clinical analysis suggests that high expression of CK2 correlates with low ING4 protein level in NSCLC. Further analysis shows that CK2 induce ING4‐S150 phosphorylation leading to ING4 ubiquitination and degradation by JFK ubiquitin ligase. In contrast, CK2 gene knockout increases ING4 protein stability and T cell activity, subsequently, inhibites NSCLC immune escape. Furthermore, the combined CK2 inhibitor with PD‐1 antibody effectively enhances antitumor immunotherapy. These findings provide a novel strategy for cancer immunotherapy. |
| first_indexed | 2024-03-09T02:16:31Z |
| format | Article |
| id | doaj.art-191955d2ee91439488c5460a23140c8e |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-09T02:16:31Z |
| publishDate | 2023-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-191955d2ee91439488c5460a23140c8e2023-12-07T04:08:35ZengWileyAdvanced Science2198-38442023-12-011034n/an/a10.1002/advs.202304068Inhibition of CK2/ING4 Pathway Facilitates Non‐Small Cell Lung Cancer ImmunotherapyQian Gou0Huiqing Chen1Mingjun Chen2Juanjuan Shi3Jianhua Jin4Qian Liu5Yongzhong Hou6Department of Oncology, the Affiliated Wujin Hospital of Jiangsu University Changzhou Jiangsu 213017 P. R. ChinaSchool of Life Science Jiangsu University Zhenjiang Jiangsu 212013 P. R. ChinaSchool of Life Science Jiangsu University Zhenjiang Jiangsu 212013 P. R. ChinaSchool of Life Science Jiangsu University Zhenjiang Jiangsu 212013 P. R. ChinaDepartment of Oncology, the Affiliated Wujin Hospital of Jiangsu University Changzhou Jiangsu 213017 P. R. ChinaDepartment of Oncology, the Affiliated Wujin Hospital of Jiangsu University Changzhou Jiangsu 213017 P. R. ChinaSchool of Life Science Jiangsu University Zhenjiang Jiangsu 212013 P. R. ChinaAbstract Immune cells can protect against tumor progression by killing cancer cells, while aberrant expression of the immune checkpoint protein PD‐L1 (programmed death ligand 1) in cancer cells facilitates tumor immune escape and inhibits anti‐tumor immunotherapy. As a serine/threonine kinase, CK2 (casein kinase 2) regulates tumor progression by multiple pathways, while it is still unclear the effect of CK2 on tumor immune escape. Here it is found that ING4 induced PD‐L1 autophagic degradation and inhibites non‐small cell lung cancer (NSCLC) immune escape by increasing T cell activity. However, clinical analysis suggests that high expression of CK2 correlates with low ING4 protein level in NSCLC. Further analysis shows that CK2 induce ING4‐S150 phosphorylation leading to ING4 ubiquitination and degradation by JFK ubiquitin ligase. In contrast, CK2 gene knockout increases ING4 protein stability and T cell activity, subsequently, inhibites NSCLC immune escape. Furthermore, the combined CK2 inhibitor with PD‐1 antibody effectively enhances antitumor immunotherapy. These findings provide a novel strategy for cancer immunotherapy.https://doi.org/10.1002/advs.202304068CK2ING4NSCLCPD‐1/PD‐L1tumor immune escape |
| spellingShingle | Qian Gou Huiqing Chen Mingjun Chen Juanjuan Shi Jianhua Jin Qian Liu Yongzhong Hou Inhibition of CK2/ING4 Pathway Facilitates Non‐Small Cell Lung Cancer Immunotherapy Advanced Science CK2 ING4 NSCLC PD‐1/PD‐L1 tumor immune escape |
| title | Inhibition of CK2/ING4 Pathway Facilitates Non‐Small Cell Lung Cancer Immunotherapy |
| title_full | Inhibition of CK2/ING4 Pathway Facilitates Non‐Small Cell Lung Cancer Immunotherapy |
| title_fullStr | Inhibition of CK2/ING4 Pathway Facilitates Non‐Small Cell Lung Cancer Immunotherapy |
| title_full_unstemmed | Inhibition of CK2/ING4 Pathway Facilitates Non‐Small Cell Lung Cancer Immunotherapy |
| title_short | Inhibition of CK2/ING4 Pathway Facilitates Non‐Small Cell Lung Cancer Immunotherapy |
| title_sort | inhibition of ck2 ing4 pathway facilitates non small cell lung cancer immunotherapy |
| topic | CK2 ING4 NSCLC PD‐1/PD‐L1 tumor immune escape |
| url | https://doi.org/10.1002/advs.202304068 |
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