Direct identification of HLA class I and class II-restricted T cell epitopes in pancreatic cancer tissues by mass spectrometry
Abstract Background Identifying T cell epitopes on pancreatic ductal adenocarcinoma (PDAC) associated antigens or neoantigens has been a challenge. In this study, we attempted to identify PDAC T cell epitopes by mass spectrometry (MS). Methods We isolated HLA class I (HLA-I) and HLA class II (HLA-II...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-10-01
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| Series: | Journal of Hematology & Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13045-022-01373-6 |
| _version_ | 1811335060051197952 |
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| author | Kenji Fujiwara Yingkuan Shao Nan Niu Tengyi Zhang Brian Herbst Mackenzie Henderson Stephen Muth Pingbo Zhang Lei Zheng |
| author_facet | Kenji Fujiwara Yingkuan Shao Nan Niu Tengyi Zhang Brian Herbst Mackenzie Henderson Stephen Muth Pingbo Zhang Lei Zheng |
| author_sort | Kenji Fujiwara |
| collection | DOAJ |
| description | Abstract Background Identifying T cell epitopes on pancreatic ductal adenocarcinoma (PDAC) associated antigens or neoantigens has been a challenge. In this study, we attempted to identify PDAC T cell epitopes by mass spectrometry (MS). Methods We isolated HLA class I (HLA-I) and HLA class II (HLA-II)-restricted peptides, respectively, from tissues of human PDAC by using the pan-HLA-I or pan-HLA-II affinity purification column and identified T cell epitopes by peptidome analysis with MS. Results Through peptidome analysis, we identified T cell epitopes shared by multiple patients with different HLA types and those containing sequences of both anti-HLA-I and HLA-II antibodies-affinity purified peptides. The identified epitopes bound non-matched HLA molecules and induced T cell response in peripheral T cells from both HLA-type matched and non-matched patients. Peptides containing both HLA class I and class II epitopes were able to induce polyfunctional cytokine responses in peripheral T cells. Conclusions T cell epitopes in PDAC can be discovered by the MS approach and can be designed into vaccine and TCR-T cell therapies for both HLA-type matched and non-matched patients. |
| first_indexed | 2024-04-13T17:18:25Z |
| format | Article |
| id | doaj.art-55e292b387044fd2aed850ced5ae6fdc |
| institution | Directory Open Access Journal |
| issn | 1756-8722 |
| language | English |
| last_indexed | 2024-04-13T17:18:25Z |
| publishDate | 2022-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Hematology & Oncology |
| spelling | doaj.art-55e292b387044fd2aed850ced5ae6fdc2022-12-22T02:38:04ZengBMCJournal of Hematology & Oncology1756-87222022-10-011511510.1186/s13045-022-01373-6Direct identification of HLA class I and class II-restricted T cell epitopes in pancreatic cancer tissues by mass spectrometryKenji Fujiwara0Yingkuan Shao1Nan Niu2Tengyi Zhang3Brian Herbst4Mackenzie Henderson5Stephen Muth6Pingbo Zhang7Lei Zheng8Department of Oncology, Johns Hopkins University School of MedicineDepartment of Oncology, Johns Hopkins University School of MedicineDepartment of Oncology, Johns Hopkins University School of MedicineDepartment of Oncology, Johns Hopkins University School of MedicineDepartment of Oncology, Johns Hopkins University School of MedicineDepartment of Oncology, Johns Hopkins University School of MedicineDepartment of Oncology, Johns Hopkins University School of MedicineDepartment of Ophthalmology, Johns Hopkins University School of MedicineDepartment of Oncology, Johns Hopkins University School of MedicineAbstract Background Identifying T cell epitopes on pancreatic ductal adenocarcinoma (PDAC) associated antigens or neoantigens has been a challenge. In this study, we attempted to identify PDAC T cell epitopes by mass spectrometry (MS). Methods We isolated HLA class I (HLA-I) and HLA class II (HLA-II)-restricted peptides, respectively, from tissues of human PDAC by using the pan-HLA-I or pan-HLA-II affinity purification column and identified T cell epitopes by peptidome analysis with MS. Results Through peptidome analysis, we identified T cell epitopes shared by multiple patients with different HLA types and those containing sequences of both anti-HLA-I and HLA-II antibodies-affinity purified peptides. The identified epitopes bound non-matched HLA molecules and induced T cell response in peripheral T cells from both HLA-type matched and non-matched patients. Peptides containing both HLA class I and class II epitopes were able to induce polyfunctional cytokine responses in peripheral T cells. Conclusions T cell epitopes in PDAC can be discovered by the MS approach and can be designed into vaccine and TCR-T cell therapies for both HLA-type matched and non-matched patients.https://doi.org/10.1186/s13045-022-01373-6Pancreatic ductal adenocarcinomaMass spectrometryT cell epitopesPeptidome analysisImmunotherapy |
| spellingShingle | Kenji Fujiwara Yingkuan Shao Nan Niu Tengyi Zhang Brian Herbst Mackenzie Henderson Stephen Muth Pingbo Zhang Lei Zheng Direct identification of HLA class I and class II-restricted T cell epitopes in pancreatic cancer tissues by mass spectrometry Journal of Hematology & Oncology Pancreatic ductal adenocarcinoma Mass spectrometry T cell epitopes Peptidome analysis Immunotherapy |
| title | Direct identification of HLA class I and class II-restricted T cell epitopes in pancreatic cancer tissues by mass spectrometry |
| title_full | Direct identification of HLA class I and class II-restricted T cell epitopes in pancreatic cancer tissues by mass spectrometry |
| title_fullStr | Direct identification of HLA class I and class II-restricted T cell epitopes in pancreatic cancer tissues by mass spectrometry |
| title_full_unstemmed | Direct identification of HLA class I and class II-restricted T cell epitopes in pancreatic cancer tissues by mass spectrometry |
| title_short | Direct identification of HLA class I and class II-restricted T cell epitopes in pancreatic cancer tissues by mass spectrometry |
| title_sort | direct identification of hla class i and class ii restricted t cell epitopes in pancreatic cancer tissues by mass spectrometry |
| topic | Pancreatic ductal adenocarcinoma Mass spectrometry T cell epitopes Peptidome analysis Immunotherapy |
| url | https://doi.org/10.1186/s13045-022-01373-6 |
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