NANOG confers resistance to complement-dependent cytotoxicity in immune-edited tumor cells through up-regulating CD59
Abstract Cancer immunoediting drives the adaptation of tumor cells to host immune surveillance. Previously, we have demonstrated that immunoediting driven by cytotoxic T lymphocytes (CTLs) enriches NANOG+ tumor cells with immune-refractory properties. Here, we found that CTL-mediated immune pressure...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-12692-6 |
| _version_ | 1811258674923962368 |
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| author | Sung Wook Son Eunho Cho Hanbyoul Cho Seon Rang Woo Hyo-Jung Lee Se Jin Oh Suyeon Kim Jae-Hoon Kim Eun Joo Chung Joon-Yong Chung Min Gyu Kim Kwon-Ho Song Tae Woo Kim |
| author_facet | Sung Wook Son Eunho Cho Hanbyoul Cho Seon Rang Woo Hyo-Jung Lee Se Jin Oh Suyeon Kim Jae-Hoon Kim Eun Joo Chung Joon-Yong Chung Min Gyu Kim Kwon-Ho Song Tae Woo Kim |
| author_sort | Sung Wook Son |
| collection | DOAJ |
| description | Abstract Cancer immunoediting drives the adaptation of tumor cells to host immune surveillance. Previously, we have demonstrated that immunoediting driven by cytotoxic T lymphocytes (CTLs) enriches NANOG+ tumor cells with immune-refractory properties. Here, we found that CTL-mediated immune pressure triggered cross-resistance of tumor cells to the complement system, a part of the innate immune system. In this process, NANOG upregulated the membrane-bound complement regulatory protein (mCRP) CD59 through promoter occupancy, thereby contributing to the resistance of tumor cells against complement-dependent cytotoxicity (CDC). Notably, targeting of NANOG sensitized the immune-refractory tumor cells to trastuzumab-mediated CDC. Collectively, our results revealed a possible mechanism through which selection imposed by T-cell based immunotherapy triggered complement-resistant phenotypes in the tumor microenvironment (TME), by establishing a firm molecular link between NANOG and CD59 in immune-edited tumor cells. We believe these results hold important implications for the clinical application of CDC-mediated therapeutic antibody. |
| first_indexed | 2024-04-12T18:18:13Z |
| format | Article |
| id | doaj.art-ba135651cfcf41238c5afc965403628b |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-12T18:18:13Z |
| publishDate | 2022-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-ba135651cfcf41238c5afc965403628b2022-12-22T03:21:32ZengNature PortfolioScientific Reports2045-23222022-05-0112111010.1038/s41598-022-12692-6NANOG confers resistance to complement-dependent cytotoxicity in immune-edited tumor cells through up-regulating CD59Sung Wook Son0Eunho Cho1Hanbyoul Cho2Seon Rang Woo3Hyo-Jung Lee4Se Jin Oh5Suyeon Kim6Jae-Hoon Kim7Eun Joo Chung8Joon-Yong Chung9Min Gyu Kim10Kwon-Ho Song11Tae Woo Kim12Department of Cell Biology, Daegu Catholic University School of MedicineDepartment of Biochemistry and Molecular Biology, Korea University College of MedicineDepartment of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of MedicineDepartment of Biochemistry and Molecular Biology, Korea University College of MedicineDepartment of Biochemistry and Molecular Biology, Korea University College of MedicineDepartment of Biochemistry and Molecular Biology, Korea University College of MedicineDepartment of Biochemistry and Molecular Biology, Korea University College of MedicineDepartment of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of MedicineRadiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of HealthMolecular Imaging Branch, Center for Cancer Research, National Cancer Institute, National Institutes of HealthSchool of Medicine, The Catholic University of KoreaDepartment of Cell Biology, Daegu Catholic University School of MedicineDepartment of Biochemistry and Molecular Biology, Korea University College of MedicineAbstract Cancer immunoediting drives the adaptation of tumor cells to host immune surveillance. Previously, we have demonstrated that immunoediting driven by cytotoxic T lymphocytes (CTLs) enriches NANOG+ tumor cells with immune-refractory properties. Here, we found that CTL-mediated immune pressure triggered cross-resistance of tumor cells to the complement system, a part of the innate immune system. In this process, NANOG upregulated the membrane-bound complement regulatory protein (mCRP) CD59 through promoter occupancy, thereby contributing to the resistance of tumor cells against complement-dependent cytotoxicity (CDC). Notably, targeting of NANOG sensitized the immune-refractory tumor cells to trastuzumab-mediated CDC. Collectively, our results revealed a possible mechanism through which selection imposed by T-cell based immunotherapy triggered complement-resistant phenotypes in the tumor microenvironment (TME), by establishing a firm molecular link between NANOG and CD59 in immune-edited tumor cells. We believe these results hold important implications for the clinical application of CDC-mediated therapeutic antibody.https://doi.org/10.1038/s41598-022-12692-6 |
| spellingShingle | Sung Wook Son Eunho Cho Hanbyoul Cho Seon Rang Woo Hyo-Jung Lee Se Jin Oh Suyeon Kim Jae-Hoon Kim Eun Joo Chung Joon-Yong Chung Min Gyu Kim Kwon-Ho Song Tae Woo Kim NANOG confers resistance to complement-dependent cytotoxicity in immune-edited tumor cells through up-regulating CD59 Scientific Reports |
| title | NANOG confers resistance to complement-dependent cytotoxicity in immune-edited tumor cells through up-regulating CD59 |
| title_full | NANOG confers resistance to complement-dependent cytotoxicity in immune-edited tumor cells through up-regulating CD59 |
| title_fullStr | NANOG confers resistance to complement-dependent cytotoxicity in immune-edited tumor cells through up-regulating CD59 |
| title_full_unstemmed | NANOG confers resistance to complement-dependent cytotoxicity in immune-edited tumor cells through up-regulating CD59 |
| title_short | NANOG confers resistance to complement-dependent cytotoxicity in immune-edited tumor cells through up-regulating CD59 |
| title_sort | nanog confers resistance to complement dependent cytotoxicity in immune edited tumor cells through up regulating cd59 |
| url | https://doi.org/10.1038/s41598-022-12692-6 |
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