Isolation of a tumor neoantigen specific CD8+ TCR from a skin biopsy of a vaccination site
T cells that recognize tumor-specific mutations are crucial for cancer immunosurveillance and in adoptive transfer of TILs or transgenic-TCR T cell products. However, their challenging identification and isolation limits their use in clinical practice. Therefore, novel approaches to isolate tumor-sp...
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Taylor & Francis Group
2025-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2025.2457793 |
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| author | Maria Paula Roberti Pornpimol Charoentong Yanhong Lyu Marten Meyer Stefan B. Eichmüller Patrick Schmidt Frank Momburg Miray Cetin Felix Hartmann Nektarios A. Valous Albrecht Stenzinger Laura Michel Peter Lichter Andreas Schneeweiss Verena Thewes Carlo Fremd Inka Zörnig Dirk Jäger |
| author_facet | Maria Paula Roberti Pornpimol Charoentong Yanhong Lyu Marten Meyer Stefan B. Eichmüller Patrick Schmidt Frank Momburg Miray Cetin Felix Hartmann Nektarios A. Valous Albrecht Stenzinger Laura Michel Peter Lichter Andreas Schneeweiss Verena Thewes Carlo Fremd Inka Zörnig Dirk Jäger |
| author_sort | Maria Paula Roberti |
| collection | DOAJ |
| description | T cells that recognize tumor-specific mutations are crucial for cancer immunosurveillance and in adoptive transfer of TILs or transgenic-TCR T cell products. However, their challenging identification and isolation limits their use in clinical practice. Therefore, novel approaches to isolate tumor-specific T cells are needed. Here, we report the isolation of neoantigen-specific CD8+ T cells from a vaccination site of a metastatic breast cancer patient who received a personalized vaccine. Based on the somatic mutations, potential MHC binding epitopes were predicted, of which 17 were selected to generate a peptide vaccine. Cutaneous biopsies were processed after the fifth vaccination cycle to obtain infiltrating lymphocytes from the vaccination site (VILs). IFNγ ELISpot revealed reactivity to four peptides used in the vaccine. Reactive T cells from VILs were non-overlapping with those detected in the blood and the tumor-microenvironment. ScTCR Seq analysis revealed the presence of a clonotype in VILs that further expanded after a round of in vitro stimulation and validated to be specific against a private mutation, namely NCOR1L1475R, presented in the context of HLA-B * 07:02, with no reactivity to the wild-type peptide. Our study shows, for the first time, that tumor mutation – specific T cells are generated at high frequencies in the vaccination site and can be isolated with standard methods for TCR screening. The easy and safe accessibility of skin biopsies overcomes the major hurdles of current TCR screening approaches and present exciting opportunities for the development of innovative immunotherapeutic strategies. |
| format | Article |
| id | doaj-art-283c0f2683f54c969b424ed81c62107e |
| institution | Kabale University |
| issn | 2162-402X |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-283c0f2683f54c969b424ed81c62107e2025-02-04T13:26:25ZengTaylor & Francis GroupOncoImmunology2162-402X2025-12-0114110.1080/2162402X.2025.2457793Isolation of a tumor neoantigen specific CD8+ TCR from a skin biopsy of a vaccination siteMaria Paula Roberti0Pornpimol Charoentong1Yanhong Lyu2Marten Meyer3Stefan B. Eichmüller4Patrick Schmidt5Frank Momburg6Miray Cetin7Felix Hartmann8Nektarios A. Valous9Albrecht Stenzinger10Laura Michel11Peter Lichter12Andreas Schneeweiss13Verena Thewes14Carlo Fremd15Inka Zörnig16Dirk Jäger17Clinical Cooperation Unit Applied Tumor Immunity, German Cancer Research Center (DKFZ), Heidelberg, GermanyClinical Cooperation Unit Applied Tumor Immunity, German Cancer Research Center (DKFZ), Heidelberg, GermanyMedical Faculty Heidelberg, Department of Medical Oncology and Internal Medicine VI, Heidelberg University Hospital, Heidelberg University, Heidelberg, GermanyClinical Cooperation Unit Applied Tumor Immunity, German Cancer Research Center (DKFZ), Heidelberg, GermanyGMP and T Cell Therapy, German Cancer Research Center (DKFZ), Heidelberg, GermanyMedical Faculty Heidelberg, Department of Medical Oncology and Internal Medicine VI, Heidelberg University Hospital, Heidelberg University, Heidelberg, GermanyClinical Cooperation Unit Applied Tumor Immunity, German Cancer Research Center (DKFZ), Heidelberg, GermanySystems Immunology and Single Cell Biology Group, German Cancer Research Center (DKFZ), Heidelberg, GermanySystems Immunology and Single Cell Biology Group, German Cancer Research Center (DKFZ), Heidelberg, GermanyClinical Cooperation Unit Applied Tumor Immunity, German Cancer Research Center (DKFZ), Heidelberg, GermanyInstitute of Pathology, University Hospital Heidelberg, Heidelberg, GermanyMedical Faculty Heidelberg, Department of Medical Oncology and Internal Medicine VI, Heidelberg University Hospital, Heidelberg University, Heidelberg, GermanyNational Center for Tumor Diseases (NCT) Heidelberg, A partnership between DKFZ and Heidelberg University Medical Center, Heidelberg, GermanyDivision of Gynecological Oncology, National Center for Tumor Diseases (NCT), A partnership between DKFZ and Heidelberg University Medical Center, Heidelberg University Hospital, Heidelberg, GermanyNational Center for Tumor Diseases (NCT) Heidelberg, A partnership between DKFZ and Heidelberg University Medical Center, Heidelberg, GermanyMedical Faculty Heidelberg, Department of Medical Oncology and Internal Medicine VI, Heidelberg University Hospital, Heidelberg University, Heidelberg, GermanyClinical Cooperation Unit Applied Tumor Immunity, German Cancer Research Center (DKFZ), Heidelberg, GermanyClinical Cooperation Unit Applied Tumor Immunity, German Cancer Research Center (DKFZ), Heidelberg, GermanyT cells that recognize tumor-specific mutations are crucial for cancer immunosurveillance and in adoptive transfer of TILs or transgenic-TCR T cell products. However, their challenging identification and isolation limits their use in clinical practice. Therefore, novel approaches to isolate tumor-specific T cells are needed. Here, we report the isolation of neoantigen-specific CD8+ T cells from a vaccination site of a metastatic breast cancer patient who received a personalized vaccine. Based on the somatic mutations, potential MHC binding epitopes were predicted, of which 17 were selected to generate a peptide vaccine. Cutaneous biopsies were processed after the fifth vaccination cycle to obtain infiltrating lymphocytes from the vaccination site (VILs). IFNγ ELISpot revealed reactivity to four peptides used in the vaccine. Reactive T cells from VILs were non-overlapping with those detected in the blood and the tumor-microenvironment. ScTCR Seq analysis revealed the presence of a clonotype in VILs that further expanded after a round of in vitro stimulation and validated to be specific against a private mutation, namely NCOR1L1475R, presented in the context of HLA-B * 07:02, with no reactivity to the wild-type peptide. Our study shows, for the first time, that tumor mutation – specific T cells are generated at high frequencies in the vaccination site and can be isolated with standard methods for TCR screening. The easy and safe accessibility of skin biopsies overcomes the major hurdles of current TCR screening approaches and present exciting opportunities for the development of innovative immunotherapeutic strategies.https://www.tandfonline.com/doi/10.1080/2162402X.2025.2457793Breast canceradoptive T cell therapyneoantigenT cell receptor engineered T cellspeptide vaccinevaccination site infiltrating lymphocytes |
| spellingShingle | Maria Paula Roberti Pornpimol Charoentong Yanhong Lyu Marten Meyer Stefan B. Eichmüller Patrick Schmidt Frank Momburg Miray Cetin Felix Hartmann Nektarios A. Valous Albrecht Stenzinger Laura Michel Peter Lichter Andreas Schneeweiss Verena Thewes Carlo Fremd Inka Zörnig Dirk Jäger Isolation of a tumor neoantigen specific CD8+ TCR from a skin biopsy of a vaccination site OncoImmunology Breast cancer adoptive T cell therapy neoantigen T cell receptor engineered T cells peptide vaccine vaccination site infiltrating lymphocytes |
| title | Isolation of a tumor neoantigen specific CD8+ TCR from a skin biopsy of a vaccination site |
| title_full | Isolation of a tumor neoantigen specific CD8+ TCR from a skin biopsy of a vaccination site |
| title_fullStr | Isolation of a tumor neoantigen specific CD8+ TCR from a skin biopsy of a vaccination site |
| title_full_unstemmed | Isolation of a tumor neoantigen specific CD8+ TCR from a skin biopsy of a vaccination site |
| title_short | Isolation of a tumor neoantigen specific CD8+ TCR from a skin biopsy of a vaccination site |
| title_sort | isolation of a tumor neoantigen specific cd8 tcr from a skin biopsy of a vaccination site |
| topic | Breast cancer adoptive T cell therapy neoantigen T cell receptor engineered T cells peptide vaccine vaccination site infiltrating lymphocytes |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2025.2457793 |
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