TCR Analyses of Two Vast and Shared Melanoma Antigen-Specific T Cell Repertoires: Common and Specific Features
Among Immunotherapeutic approaches for cancer treatment, the adoptive transfer of antigen specific T cells is still a relevant approach, that could have higher efficacy when further combined with immune check-point blockade. A high number of adoptive transfer trials have been performed in metastatic...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.01962/full |
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| author | Sylvain Simon Sylvain Simon Zhong Wu J. Cruard J. Cruard Virginie Vignard Virginie Vignard Virginie Vignard Agnes Fortun Agnes Fortun Amir Khammari Amir Khammari Amir Khammari Brigitte Dreno Brigitte Dreno Brigitte Dreno Francois Lang Francois Lang Samuel J. Rulli Nathalie Labarriere Nathalie Labarriere Nathalie Labarriere |
| author_facet | Sylvain Simon Sylvain Simon Zhong Wu J. Cruard J. Cruard Virginie Vignard Virginie Vignard Virginie Vignard Agnes Fortun Agnes Fortun Amir Khammari Amir Khammari Amir Khammari Brigitte Dreno Brigitte Dreno Brigitte Dreno Francois Lang Francois Lang Samuel J. Rulli Nathalie Labarriere Nathalie Labarriere Nathalie Labarriere |
| author_sort | Sylvain Simon |
| collection | DOAJ |
| description | Among Immunotherapeutic approaches for cancer treatment, the adoptive transfer of antigen specific T cells is still a relevant approach, that could have higher efficacy when further combined with immune check-point blockade. A high number of adoptive transfer trials have been performed in metastatic melanoma, due to its high immunogenic potential, either with polyclonal TIL or antigen-specific polyclonal populations. In this setting, the extensive characterization of T cell functions and receptor diversity of infused polyclonal T cells is required, notably for monitoring purposes. We developed a clinical grade procedure for the selection and amplification of polyclonal CD8 T cells, specific for two shared and widely expressed melanoma antigens: Melan-A and MELOE-1. This procedure is currently used in a clinical trial for HLA-A2 metastatic melanoma patients. In this study, we characterized the T-cell diversity (T-cell repertoire) of such T cell populations using a new RNAseq strategy. We first assessed the added-value of TCR receptor sequencing, in terms of sensitivity and specificity, by direct comparison with cytometry analysis of the T cell populations labeled with anti-Vß-specific antibodies. Results from these analyzes also confirmed specific features already reported for Melan-A and MELOE-1 specific T cell repertoires in terms of V-alpha recurrence usage, on a very high number of T cell clonotypes. Furthermore, these analyses also revealed undescribed features, such as the recurrence of a specific motif in the CDR3α region for MELOE-1 specific T cell repertoire. Finally, the analysis of a large number of T cell clonotypes originating from various patients revealed the existence of public CDR3α and ß clonotypes for Melan-A and MELOE-1 specific T cells. In conclusion, this method of high throughput TCR sequencing is a reliable and powerful approach to deeply characterize polyclonal T cell repertoires, and to reveal specific features of a given TCR repertoire, that would be useful for immune follow-up of cancer patients treated by immunotherapeutic approaches. |
| first_indexed | 2024-12-20T14:39:36Z |
| format | Article |
| id | doaj.art-3fcadf62073e44acb63c75d632689c8d |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-20T14:39:36Z |
| publishDate | 2018-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-3fcadf62073e44acb63c75d632689c8d2022-12-21T19:37:20ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-08-01910.3389/fimmu.2018.01962408379TCR Analyses of Two Vast and Shared Melanoma Antigen-Specific T Cell Repertoires: Common and Specific FeaturesSylvain Simon0Sylvain Simon1Zhong Wu2J. Cruard3J. Cruard4Virginie Vignard5Virginie Vignard6Virginie Vignard7Agnes Fortun8Agnes Fortun9Amir Khammari10Amir Khammari11Amir Khammari12Brigitte Dreno13Brigitte Dreno14Brigitte Dreno15Francois Lang16Francois Lang17Samuel J. Rulli18Nathalie Labarriere19Nathalie Labarriere20Nathalie Labarriere21CRCINA, INSERM, Université d'Angers, Université de Nantes, Nantes, FranceLabEx IGO “Immunotherapy, Graft, Oncology,”Nantes, FranceQiagen Sciences, Frederick, MD, United StatesCRCINA, INSERM, Université d'Angers, Université de Nantes, Nantes, FranceLabEx IGO “Immunotherapy, Graft, Oncology,”Nantes, FranceCRCINA, INSERM, Université d'Angers, Université de Nantes, Nantes, FranceLabEx IGO “Immunotherapy, Graft, Oncology,”Nantes, FranceCentre Hospitalier Universitaire Nantes, Nantes, FranceCRCINA, INSERM, Université d'Angers, Université de Nantes, Nantes, FranceLabEx IGO “Immunotherapy, Graft, Oncology,”Nantes, FranceCRCINA, INSERM, Université d'Angers, Université de Nantes, Nantes, FranceLabEx IGO “Immunotherapy, Graft, Oncology,”Nantes, FranceDepartment of Dermato-Cancerology of Nantes Hospital, Nantes, FranceCRCINA, INSERM, Université d'Angers, Université de Nantes, Nantes, FranceLabEx IGO “Immunotherapy, Graft, Oncology,”Nantes, FranceDepartment of Dermato-Cancerology of Nantes Hospital, Nantes, FranceCRCINA, INSERM, Université d'Angers, Université de Nantes, Nantes, FranceLabEx IGO “Immunotherapy, Graft, Oncology,”Nantes, FranceQiagen Sciences, Frederick, MD, United StatesCRCINA, INSERM, Université d'Angers, Université de Nantes, Nantes, FranceLabEx IGO “Immunotherapy, Graft, Oncology,”Nantes, FranceCentre Hospitalier Universitaire Nantes, Nantes, FranceAmong Immunotherapeutic approaches for cancer treatment, the adoptive transfer of antigen specific T cells is still a relevant approach, that could have higher efficacy when further combined with immune check-point blockade. A high number of adoptive transfer trials have been performed in metastatic melanoma, due to its high immunogenic potential, either with polyclonal TIL or antigen-specific polyclonal populations. In this setting, the extensive characterization of T cell functions and receptor diversity of infused polyclonal T cells is required, notably for monitoring purposes. We developed a clinical grade procedure for the selection and amplification of polyclonal CD8 T cells, specific for two shared and widely expressed melanoma antigens: Melan-A and MELOE-1. This procedure is currently used in a clinical trial for HLA-A2 metastatic melanoma patients. In this study, we characterized the T-cell diversity (T-cell repertoire) of such T cell populations using a new RNAseq strategy. We first assessed the added-value of TCR receptor sequencing, in terms of sensitivity and specificity, by direct comparison with cytometry analysis of the T cell populations labeled with anti-Vß-specific antibodies. Results from these analyzes also confirmed specific features already reported for Melan-A and MELOE-1 specific T cell repertoires in terms of V-alpha recurrence usage, on a very high number of T cell clonotypes. Furthermore, these analyses also revealed undescribed features, such as the recurrence of a specific motif in the CDR3α region for MELOE-1 specific T cell repertoire. Finally, the analysis of a large number of T cell clonotypes originating from various patients revealed the existence of public CDR3α and ß clonotypes for Melan-A and MELOE-1 specific T cells. In conclusion, this method of high throughput TCR sequencing is a reliable and powerful approach to deeply characterize polyclonal T cell repertoires, and to reveal specific features of a given TCR repertoire, that would be useful for immune follow-up of cancer patients treated by immunotherapeutic approaches.https://www.frontiersin.org/article/10.3389/fimmu.2018.01962/fullTCR sequencingmelanomaMelan-AMELOE-1immunotherapy |
| spellingShingle | Sylvain Simon Sylvain Simon Zhong Wu J. Cruard J. Cruard Virginie Vignard Virginie Vignard Virginie Vignard Agnes Fortun Agnes Fortun Amir Khammari Amir Khammari Amir Khammari Brigitte Dreno Brigitte Dreno Brigitte Dreno Francois Lang Francois Lang Samuel J. Rulli Nathalie Labarriere Nathalie Labarriere Nathalie Labarriere TCR Analyses of Two Vast and Shared Melanoma Antigen-Specific T Cell Repertoires: Common and Specific Features Frontiers in Immunology TCR sequencing melanoma Melan-A MELOE-1 immunotherapy |
| title | TCR Analyses of Two Vast and Shared Melanoma Antigen-Specific T Cell Repertoires: Common and Specific Features |
| title_full | TCR Analyses of Two Vast and Shared Melanoma Antigen-Specific T Cell Repertoires: Common and Specific Features |
| title_fullStr | TCR Analyses of Two Vast and Shared Melanoma Antigen-Specific T Cell Repertoires: Common and Specific Features |
| title_full_unstemmed | TCR Analyses of Two Vast and Shared Melanoma Antigen-Specific T Cell Repertoires: Common and Specific Features |
| title_short | TCR Analyses of Two Vast and Shared Melanoma Antigen-Specific T Cell Repertoires: Common and Specific Features |
| title_sort | tcr analyses of two vast and shared melanoma antigen specific t cell repertoires common and specific features |
| topic | TCR sequencing melanoma Melan-A MELOE-1 immunotherapy |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.01962/full |
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