Spontaneous high clonal expansion of Wilms’ tumor gene 1-specific cytotoxic T-lymphocytes in patients with Wilms’ tumor gene 1-expressing solid tumor
Abstract Wilms’ tumor protein 1 (WT1)-targeted immunotherapy has been used in patients with leukemia and solid tumors. However, the spontaneous WT1-specific immune response before WT1 peptide vaccination in patients with WT1-expressing tumors (PTs) remains unclear. Therefore, we investigated whether...
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Springer
2024-11-01
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| Series: | Cancer Immunology, Immunotherapy |
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| Online Access: | https://doi.org/10.1007/s00262-024-03862-8 |
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| author | Soyoko Morimoto Yukie Tanaka Jun Nakata Fumihiro Fujiki Kana Hasegawa Hiroko Nakajima Sumiyuki Nishida Akihiro Tsuboi Naoki Hosen Naoki Kagawa Motohiko Maruno Akira Myoui Takayuki Enomoto Shuichi Izumoto Mitsugu Sekimoto Naoya Hashimoto Toshiki Yoshimine Atsushi Kumanogoh Yusuke Oji Yoshihiro Oka Haruo Sugiyama |
| author_facet | Soyoko Morimoto Yukie Tanaka Jun Nakata Fumihiro Fujiki Kana Hasegawa Hiroko Nakajima Sumiyuki Nishida Akihiro Tsuboi Naoki Hosen Naoki Kagawa Motohiko Maruno Akira Myoui Takayuki Enomoto Shuichi Izumoto Mitsugu Sekimoto Naoya Hashimoto Toshiki Yoshimine Atsushi Kumanogoh Yusuke Oji Yoshihiro Oka Haruo Sugiyama |
| author_sort | Soyoko Morimoto |
| collection | DOAJ |
| description | Abstract Wilms’ tumor protein 1 (WT1)-targeted immunotherapy has been used in patients with leukemia and solid tumors. However, the spontaneous WT1-specific immune response before WT1 peptide vaccination in patients with WT1-expressing tumors (PTs) remains unclear. Therefore, we investigated whether WT1-specific cytotoxic CD8+ T-lymphocytes (CTLs) are clonally expanded in the peripheral blood outside of tumor sites. Clonal expansion of WT1126 peptide (a.a.126–134)-specific CTLs (WT1126-CTLs) was compared between seven PTs and five healthy volunteers (HVs), and their T-cell receptors (TCRs) were analyzed at the single-cell level. Overall, 433 and 351 TCR β-chains of WT1126-CTLs were detected from PTs and HVs, respectively, and complementarity-determining region 3 was sequenced for clonality analysis. The frequencies of WT1126-CTLs were higher in human leukocyte antigen (HLA)-A*02:01+ PTs than in HLA-A*02:01+ HVs, although the difference was not statistically significant. WT1126-CTLs of differentiated types, including memory and effector, were higher in PTs than in HVs; whereas, those of the naïve type were higher in HVs than in PTs. WT1126-CTL clonality was significantly higher in PTs than in HVs. Furthermore, the frequency of effector WT1126-CTLs positively correlated with WT1126-CTL clonality in PTs; whereas, the frequency of naïve phenotype WT1126-CTLs tended to be negatively correlated with clonality. In conclusion, these results suggest that the WT1 protein in tumor cells is highly immunogenic, thereby stimulating endogenous naïve-type WT1126-CTLs and enabling them to clonally expand and differentiate into effector-type WT1126-CTLs. |
| format | Article |
| id | doaj-art-0a4bfd60c4fa414aa30a04225fb437f1 |
| institution | Kabale University |
| issn | 1432-0851 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Springer |
| record_format | Article |
| series | Cancer Immunology, Immunotherapy |
| spelling | doaj-art-0a4bfd60c4fa414aa30a04225fb437f12025-02-02T12:26:46ZengSpringerCancer Immunology, Immunotherapy1432-08512024-11-0174111210.1007/s00262-024-03862-8Spontaneous high clonal expansion of Wilms’ tumor gene 1-specific cytotoxic T-lymphocytes in patients with Wilms’ tumor gene 1-expressing solid tumorSoyoko Morimoto0Yukie Tanaka1Jun Nakata2Fumihiro Fujiki3Kana Hasegawa4Hiroko Nakajima5Sumiyuki Nishida6Akihiro Tsuboi7Naoki Hosen8Naoki Kagawa9Motohiko Maruno10Akira Myoui11Takayuki Enomoto12Shuichi Izumoto13Mitsugu Sekimoto14Naoya Hashimoto15Toshiki Yoshimine16Atsushi Kumanogoh17Yusuke Oji18Yoshihiro Oka19Haruo Sugiyama20Department of Cancer Stem Cell Biology, Osaka University Graduate School of MedicineDepartment of Cancer Immunotherapy, Osaka University Graduate School of MedicineDepartment of Clinical Laboratory and Biomedical Sciences, Osaka University Graduate School of MedicineDepartment of Cancer Immunotherapy, Osaka University Graduate School of MedicineLaboratory of Cellular Immunotherapy, World Premier International Research Center Initiative Immunology Frontier Research Center (WPI-IFReC), Osaka UniversityDepartment of Cancer Immunology, Osaka University Graduate School of MedicineStrategic Global Partnership & X (Cross)-Innovation Initiative Graduate School of Medicine, Osaka University and Osaka University HospitalDepartment of Cancer Immunotherapy, Osaka University Graduate School of MedicineLaboratory of Cellular Immunotherapy, World Premier International Research Center Initiative Immunology Frontier Research Center (WPI-IFReC), Osaka UniversityDepartment of Neurosurgery, Osaka University Graduate School of MedicineDepartment of Neurosurgery, Osaka University Graduate School of MedicineMedical Center for Translational Research, Department of Medical Innovation, Osaka University HospitalDepartment of Obstetrics and Gynecology, Osaka University Graduate School of MedicineDepartment of Neurosurgery, Hyogo College of MedicineDepartment of Gastroenterological Surgery Graduate School of Medicine, Osaka UniversityDepartment of Neurosurgery, Osaka University Graduate School of MedicineDepartment of Neurosurgery, Osaka University Graduate School of MedicineDepartment of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of MedicineDepartment of Clinical Laboratory and Biomedical Sciences, Osaka University Graduate School of MedicineDepartment of Cancer Stem Cell Biology, Osaka University Graduate School of MedicineDepartment of Cancer Immunology, Osaka University Graduate School of MedicineAbstract Wilms’ tumor protein 1 (WT1)-targeted immunotherapy has been used in patients with leukemia and solid tumors. However, the spontaneous WT1-specific immune response before WT1 peptide vaccination in patients with WT1-expressing tumors (PTs) remains unclear. Therefore, we investigated whether WT1-specific cytotoxic CD8+ T-lymphocytes (CTLs) are clonally expanded in the peripheral blood outside of tumor sites. Clonal expansion of WT1126 peptide (a.a.126–134)-specific CTLs (WT1126-CTLs) was compared between seven PTs and five healthy volunteers (HVs), and their T-cell receptors (TCRs) were analyzed at the single-cell level. Overall, 433 and 351 TCR β-chains of WT1126-CTLs were detected from PTs and HVs, respectively, and complementarity-determining region 3 was sequenced for clonality analysis. The frequencies of WT1126-CTLs were higher in human leukocyte antigen (HLA)-A*02:01+ PTs than in HLA-A*02:01+ HVs, although the difference was not statistically significant. WT1126-CTLs of differentiated types, including memory and effector, were higher in PTs than in HVs; whereas, those of the naïve type were higher in HVs than in PTs. WT1126-CTL clonality was significantly higher in PTs than in HVs. Furthermore, the frequency of effector WT1126-CTLs positively correlated with WT1126-CTL clonality in PTs; whereas, the frequency of naïve phenotype WT1126-CTLs tended to be negatively correlated with clonality. In conclusion, these results suggest that the WT1 protein in tumor cells is highly immunogenic, thereby stimulating endogenous naïve-type WT1126-CTLs and enabling them to clonally expand and differentiate into effector-type WT1126-CTLs.https://doi.org/10.1007/s00262-024-03862-8WT1WT1126-CTLsSingle-cellTCR repertoireClonality |
| spellingShingle | Soyoko Morimoto Yukie Tanaka Jun Nakata Fumihiro Fujiki Kana Hasegawa Hiroko Nakajima Sumiyuki Nishida Akihiro Tsuboi Naoki Hosen Naoki Kagawa Motohiko Maruno Akira Myoui Takayuki Enomoto Shuichi Izumoto Mitsugu Sekimoto Naoya Hashimoto Toshiki Yoshimine Atsushi Kumanogoh Yusuke Oji Yoshihiro Oka Haruo Sugiyama Spontaneous high clonal expansion of Wilms’ tumor gene 1-specific cytotoxic T-lymphocytes in patients with Wilms’ tumor gene 1-expressing solid tumor Cancer Immunology, Immunotherapy WT1 WT1126-CTLs Single-cell TCR repertoire Clonality |
| title | Spontaneous high clonal expansion of Wilms’ tumor gene 1-specific cytotoxic T-lymphocytes in patients with Wilms’ tumor gene 1-expressing solid tumor |
| title_full | Spontaneous high clonal expansion of Wilms’ tumor gene 1-specific cytotoxic T-lymphocytes in patients with Wilms’ tumor gene 1-expressing solid tumor |
| title_fullStr | Spontaneous high clonal expansion of Wilms’ tumor gene 1-specific cytotoxic T-lymphocytes in patients with Wilms’ tumor gene 1-expressing solid tumor |
| title_full_unstemmed | Spontaneous high clonal expansion of Wilms’ tumor gene 1-specific cytotoxic T-lymphocytes in patients with Wilms’ tumor gene 1-expressing solid tumor |
| title_short | Spontaneous high clonal expansion of Wilms’ tumor gene 1-specific cytotoxic T-lymphocytes in patients with Wilms’ tumor gene 1-expressing solid tumor |
| title_sort | spontaneous high clonal expansion of wilms tumor gene 1 specific cytotoxic t lymphocytes in patients with wilms tumor gene 1 expressing solid tumor |
| topic | WT1 WT1126-CTLs Single-cell TCR repertoire Clonality |
| url | https://doi.org/10.1007/s00262-024-03862-8 |
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