Dynamics of Melanoma-Associated Epitope-Specific CD8+ T Cells in the Blood Correlate With Clinical Outcome Under PD-1 Blockade
Immune checkpoint blockade (ICB) is standard-of-care for patients with metastatic melanoma. It may re-invigorate T cells recognizing tumors, and several tumor antigens have been identified as potential targets. However, little is known about the dynamics of tumor antigen-specific T cells in the circ...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.906352/full |
| _version_ | 1818113259873501184 |
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| author | Andrea Gaißler Andrea Gaißler Trine Sundebo Meldgaard Christina Heeke Sepideh Babaei Siri Amanda Tvingsholm Jonas Bochem Jonas Bochem Janine Spreuer Janine Spreuer Teresa Amaral Teresa Amaral Nikolaus Benjamin Wagner Nikolaus Benjamin Wagner Reinhild Klein Friedegund Meier Friedegund Meier Claus Garbe Thomas K. Eigentler Graham Pawelec Graham Pawelec Manfred Claassen Manfred Claassen Benjamin Weide Sine Reker Hadrup Kilian Wistuba-Hamprecht Kilian Wistuba-Hamprecht Kilian Wistuba-Hamprecht |
| author_facet | Andrea Gaißler Andrea Gaißler Trine Sundebo Meldgaard Christina Heeke Sepideh Babaei Siri Amanda Tvingsholm Jonas Bochem Jonas Bochem Janine Spreuer Janine Spreuer Teresa Amaral Teresa Amaral Nikolaus Benjamin Wagner Nikolaus Benjamin Wagner Reinhild Klein Friedegund Meier Friedegund Meier Claus Garbe Thomas K. Eigentler Graham Pawelec Graham Pawelec Manfred Claassen Manfred Claassen Benjamin Weide Sine Reker Hadrup Kilian Wistuba-Hamprecht Kilian Wistuba-Hamprecht Kilian Wistuba-Hamprecht |
| author_sort | Andrea Gaißler |
| collection | DOAJ |
| description | Immune checkpoint blockade (ICB) is standard-of-care for patients with metastatic melanoma. It may re-invigorate T cells recognizing tumors, and several tumor antigens have been identified as potential targets. However, little is known about the dynamics of tumor antigen-specific T cells in the circulation, which might provide valuable information on ICB responses in a minimally invasive manner. Here, we investigated individual signatures composed of up to 167 different melanoma-associated epitope (MAE)-specific CD8+ T cells in the blood of stage IV melanoma patients before and during anti-PD-1 treatment, using a peptide-loaded multimer-based high-throughput approach. Additionally, checkpoint receptor expression patterns on T cell subsets and frequencies of myeloid-derived suppressor cells and regulatory T cells were quantified by flow cytometry. Regression analysis using the MAE-specific CD8+ T cell populations was applied to identify those that correlated with overall survival (OS). The abundance of MAE-specific CD8+ T cell populations, as well as their dynamics under therapy, varied between patients. Those with a dominant increase of these T cell populations during PD-1 ICB had a longer OS and progression-free survival than those with decreasing or balanced signatures. Patients with a dominantly increased MAE-specific CD8+ T cell signature also exhibited an increase in TIM-3+ and LAG-3+ T cells. From these results, we created a model predicting improved/reduced OS by combining data on dynamics of the three most informative MAE-specific CD8+ T cell populations. Our results provide insights into the dynamics of circulating MAE-specific CD8+ T cell populations during ICB, and should contribute to a better understanding of biomarkers of response and anti-cancer mechanisms. |
| first_indexed | 2024-12-11T03:32:00Z |
| format | Article |
| id | doaj.art-dc14c7a742f64dffb8f851c85b32709c |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T03:32:00Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-dc14c7a742f64dffb8f851c85b32709c2022-12-22T01:22:21ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-07-011310.3389/fimmu.2022.906352906352Dynamics of Melanoma-Associated Epitope-Specific CD8+ T Cells in the Blood Correlate With Clinical Outcome Under PD-1 BlockadeAndrea Gaißler0Andrea Gaißler1Trine Sundebo Meldgaard2Christina Heeke3Sepideh Babaei4Siri Amanda Tvingsholm5Jonas Bochem6Jonas Bochem7Janine Spreuer8Janine Spreuer9Teresa Amaral10Teresa Amaral11Nikolaus Benjamin Wagner12Nikolaus Benjamin Wagner13Reinhild Klein14Friedegund Meier15Friedegund Meier16Claus Garbe17Thomas K. Eigentler18Graham Pawelec19Graham Pawelec20Manfred Claassen21Manfred Claassen22Benjamin Weide23Sine Reker Hadrup24Kilian Wistuba-Hamprecht25Kilian Wistuba-Hamprecht26Kilian Wistuba-Hamprecht27Department of Dermatology, University Hospital Tübingen, Eberhard Karls University of Tübingen, Tübingen, GermanyInternal Medicine I, University Hospital Tübingen, Eberhard Karls University of Tübingen, Tübingen, GermanyDepartment of Health Technology, Danmarks Tekniske Universitet (DTU) HEALTH TECH, Copenhagen, DenmarkDepartment of Health Technology, Danmarks Tekniske Universitet (DTU) HEALTH TECH, Copenhagen, DenmarkInternal Medicine I, University Hospital Tübingen, Eberhard Karls University of Tübingen, Tübingen, GermanyDepartment of Health Technology, Danmarks Tekniske Universitet (DTU) HEALTH TECH, Copenhagen, DenmarkDepartment of Dermatology, University Hospital Tübingen, Eberhard Karls University of Tübingen, Tübingen, GermanyInternal Medicine I, University Hospital Tübingen, Eberhard Karls University of Tübingen, Tübingen, GermanyDepartment of Dermatology, University Hospital Tübingen, Eberhard Karls University of Tübingen, Tübingen, GermanyInternal Medicine I, University Hospital Tübingen, Eberhard Karls University of Tübingen, Tübingen, GermanyDepartment of Dermatology, University Hospital Tübingen, Eberhard Karls University of Tübingen, Tübingen, GermanyExcellence Cluster (EXC) 2180, “Image Guided and Functionally Instructed Tumor Therapies” (iFIT), Tübingen, GermanyDepartment of Dermatology, University Hospital Tübingen, Eberhard Karls University of Tübingen, Tübingen, GermanyDepartment of Dermatology, Venereology and Allergology, Kantonsspital St. Gallen, St. Gallen, SwitzerlandInternal Medicine II, University Hospital Tübingen, Eberhard Karls University of Tübingen, Tübingen, GermanySkin Cancer Center at the University Cancer Centre and National Center for Tumor Diseases Dresden, Dresden, GermanyDepartment of Dermatology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, GermanyDepartment of Dermatology, University Hospital Tübingen, Eberhard Karls University of Tübingen, Tübingen, GermanyDepartment of Dermatology, Venereology and Allergology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany0Department of Immunology, Interfaculty Institute for Cell Biology, Eberhard Karls University Tübingen, Tübingen, Germany1Health Sciences North Research Institute, Sudbury, ON, CanadaInternal Medicine I, University Hospital Tübingen, Eberhard Karls University of Tübingen, Tübingen, Germany2Department of Computer Science, Eberhard Karls University of Tübingen, Tübingen, GermanyDepartment of Dermatology, University Hospital Tübingen, Eberhard Karls University of Tübingen, Tübingen, GermanyDepartment of Health Technology, Danmarks Tekniske Universitet (DTU) HEALTH TECH, Copenhagen, DenmarkDepartment of Dermatology, University Hospital Tübingen, Eberhard Karls University of Tübingen, Tübingen, GermanyInternal Medicine I, University Hospital Tübingen, Eberhard Karls University of Tübingen, Tübingen, Germany0Department of Immunology, Interfaculty Institute for Cell Biology, Eberhard Karls University Tübingen, Tübingen, GermanyImmune checkpoint blockade (ICB) is standard-of-care for patients with metastatic melanoma. It may re-invigorate T cells recognizing tumors, and several tumor antigens have been identified as potential targets. However, little is known about the dynamics of tumor antigen-specific T cells in the circulation, which might provide valuable information on ICB responses in a minimally invasive manner. Here, we investigated individual signatures composed of up to 167 different melanoma-associated epitope (MAE)-specific CD8+ T cells in the blood of stage IV melanoma patients before and during anti-PD-1 treatment, using a peptide-loaded multimer-based high-throughput approach. Additionally, checkpoint receptor expression patterns on T cell subsets and frequencies of myeloid-derived suppressor cells and regulatory T cells were quantified by flow cytometry. Regression analysis using the MAE-specific CD8+ T cell populations was applied to identify those that correlated with overall survival (OS). The abundance of MAE-specific CD8+ T cell populations, as well as their dynamics under therapy, varied between patients. Those with a dominant increase of these T cell populations during PD-1 ICB had a longer OS and progression-free survival than those with decreasing or balanced signatures. Patients with a dominantly increased MAE-specific CD8+ T cell signature also exhibited an increase in TIM-3+ and LAG-3+ T cells. From these results, we created a model predicting improved/reduced OS by combining data on dynamics of the three most informative MAE-specific CD8+ T cell populations. Our results provide insights into the dynamics of circulating MAE-specific CD8+ T cell populations during ICB, and should contribute to a better understanding of biomarkers of response and anti-cancer mechanisms.https://www.frontiersin.org/articles/10.3389/fimmu.2022.906352/fullT cellscheckpoint blockademelanomamelanoma-associated antigenregression analysisdextramer |
| spellingShingle | Andrea Gaißler Andrea Gaißler Trine Sundebo Meldgaard Christina Heeke Sepideh Babaei Siri Amanda Tvingsholm Jonas Bochem Jonas Bochem Janine Spreuer Janine Spreuer Teresa Amaral Teresa Amaral Nikolaus Benjamin Wagner Nikolaus Benjamin Wagner Reinhild Klein Friedegund Meier Friedegund Meier Claus Garbe Thomas K. Eigentler Graham Pawelec Graham Pawelec Manfred Claassen Manfred Claassen Benjamin Weide Sine Reker Hadrup Kilian Wistuba-Hamprecht Kilian Wistuba-Hamprecht Kilian Wistuba-Hamprecht Dynamics of Melanoma-Associated Epitope-Specific CD8+ T Cells in the Blood Correlate With Clinical Outcome Under PD-1 Blockade Frontiers in Immunology T cells checkpoint blockade melanoma melanoma-associated antigen regression analysis dextramer |
| title | Dynamics of Melanoma-Associated Epitope-Specific CD8+ T Cells in the Blood Correlate With Clinical Outcome Under PD-1 Blockade |
| title_full | Dynamics of Melanoma-Associated Epitope-Specific CD8+ T Cells in the Blood Correlate With Clinical Outcome Under PD-1 Blockade |
| title_fullStr | Dynamics of Melanoma-Associated Epitope-Specific CD8+ T Cells in the Blood Correlate With Clinical Outcome Under PD-1 Blockade |
| title_full_unstemmed | Dynamics of Melanoma-Associated Epitope-Specific CD8+ T Cells in the Blood Correlate With Clinical Outcome Under PD-1 Blockade |
| title_short | Dynamics of Melanoma-Associated Epitope-Specific CD8+ T Cells in the Blood Correlate With Clinical Outcome Under PD-1 Blockade |
| title_sort | dynamics of melanoma associated epitope specific cd8 t cells in the blood correlate with clinical outcome under pd 1 blockade |
| topic | T cells checkpoint blockade melanoma melanoma-associated antigen regression analysis dextramer |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.906352/full |
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