The immune cell dynamics in the peripheral blood of cHL patients receiving anti-PD1 treatment
Checkpoint blockade therapy (CBT) involving anti-PD1 antibodies represents the standard approach for cHL patients who do not respond to second-line therapy. Nonetheless, only 20% of relapsed/refractory (R/R) cHL patients treated with CBT achieve complete remission. In this study, we extensively exam...
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Frontiers Media S.A.
2025-03-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2025.1518107/full |
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| author | Vanessa Cristaldi Lodovico Terzi di Bergamo Lodovico Terzi di Bergamo Lucrezia Patruno Marinos Kallikourdis Marinos Kallikourdis Giada Andrea Cassanmagnago Francesco Corrado Eleonora Calabretta Adalgisa Condoluci Adalgisa Condoluci Martina di Trani Daoud Rahal Gianluca Basso Clelia Peano Alex Graudenzi Alex Graudenzi Marco Antoniotti Marco Antoniotti Davide Rossi Davide Rossi Carmelo Carlo-Stella Carmelo Carlo-Stella |
| author_facet | Vanessa Cristaldi Lodovico Terzi di Bergamo Lodovico Terzi di Bergamo Lucrezia Patruno Marinos Kallikourdis Marinos Kallikourdis Giada Andrea Cassanmagnago Francesco Corrado Eleonora Calabretta Adalgisa Condoluci Adalgisa Condoluci Martina di Trani Daoud Rahal Gianluca Basso Clelia Peano Alex Graudenzi Alex Graudenzi Marco Antoniotti Marco Antoniotti Davide Rossi Davide Rossi Carmelo Carlo-Stella Carmelo Carlo-Stella |
| author_sort | Vanessa Cristaldi |
| collection | DOAJ |
| description | Checkpoint blockade therapy (CBT) involving anti-PD1 antibodies represents the standard approach for cHL patients who do not respond to second-line therapy. Nonetheless, only 20% of relapsed/refractory (R/R) cHL patients treated with CBT achieve complete remission. In this study, we extensively examined the immune dynamics in eight R/R cHL patients treated with CBT, consisting of four complete responders (CR) and four experiencing disease progression (PD), by single cell analysis of peripheral blood mononuclear cells (PBMCs). Our unique approach encompassed longitudinal analysis with three time points, providing a comprehensive understanding of the evolving immune responses during anti-PD1 therapy. Through gene expression profiling, we identified a stable and distinctive KLRG1+/FOS+/JUN+/GZMA+/CD8+ T cell phenotype in patients achieving complete responses. This specific CD8+ T cell subset exhibited sustained activation, underscoring its potential pivotal role in mounting an effective immune response against cHL. Furthermore, T cell receptor (TCR) analysis revealed that in responder patients there is clonal expansion between TCR clonotypes specifically in the KLRG1+/FOS+/JUN+/GZMA+/CD8+ T cell subset. Our longitudinal study offers unique insights into the complex immune dynamics of multiply relapsed/highly pre-treated cHL patients undergoing anti-PD1 therapy. |
| format | Article |
| id | doaj-art-369a14e1aa844e42a99d8bcf8b1a9e05 |
| institution | DOAJ |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-369a14e1aa844e42a99d8bcf8b1a9e052025-08-20T02:52:45ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-03-011510.3389/fonc.2025.15181071518107The immune cell dynamics in the peripheral blood of cHL patients receiving anti-PD1 treatmentVanessa Cristaldi0Lodovico Terzi di Bergamo1Lodovico Terzi di Bergamo2Lucrezia Patruno3Marinos Kallikourdis4Marinos Kallikourdis5Giada Andrea Cassanmagnago6Francesco Corrado7Eleonora Calabretta8Adalgisa Condoluci9Adalgisa Condoluci10Martina di Trani11Daoud Rahal12Gianluca Basso13Clelia Peano14Alex Graudenzi15Alex Graudenzi16Marco Antoniotti17Marco Antoniotti18Davide Rossi19Davide Rossi20Carmelo Carlo-Stella21Carmelo Carlo-Stella22Department of Biomedical Sciences, Humanitas University, Milano, ItalyLaboratory of Experimental Hematology, Institute of Oncology Research, Bellinzona, SwitzerlandDepartment of Health Science and Technology, Swiss Federal Institute of Technology (ETH Zürich), Zurich, SwitzerlandDepartment of Informatics, Systems and Communication of the University of Milan-Bicocca, Milan, ItalyDepartment of Biomedical Sciences, Humanitas University, Milano, ItalyAdaptive Immunity Lab, IRCCS Humanitas Research Hospital, Milan, ItalyDepartment of Biomedical Sciences, Humanitas University, Milano, ItalyDepartment of Oncology and Hematology, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Milan, ItalyDepartment of Oncology and Hematology, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Milan, ItalyLaboratory of Experimental Hematology, Institute of Oncology Research, Bellinzona, SwitzerlandOncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, SwitzerlandDepartment of Biomedical Sciences, Humanitas University, Milano, ItalyDepartment of Pathology, IRCCS Humanitas Research Hospital, Milan, ItalyDepartment of Biomedical Sciences, Humanitas University, Milano, ItalyInstitute of Genetics and Biomedical Research, UoS of Milan, National Research Council, Milan, Italy0Institute of Molecular Bioimaging and Physiology, Consiglio Nazionale delle Ricerche (IBFM-CNR), Milan, Italy1Bicocca Bioinformatics, Biostatistic, Bioimaging Centre (B4), Università degli Studi di Milano-Bicocca, Milan, ItalyDepartment of Informatics, Systems and Communication of the University of Milan-Bicocca, Milan, Italy1Bicocca Bioinformatics, Biostatistic, Bioimaging Centre (B4), Università degli Studi di Milano-Bicocca, Milan, ItalyLaboratory of Experimental Hematology, Institute of Oncology Research, Bellinzona, SwitzerlandOncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, SwitzerlandDepartment of Biomedical Sciences, Humanitas University, Milano, ItalyDepartment of Oncology and Hematology, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Milan, ItalyCheckpoint blockade therapy (CBT) involving anti-PD1 antibodies represents the standard approach for cHL patients who do not respond to second-line therapy. Nonetheless, only 20% of relapsed/refractory (R/R) cHL patients treated with CBT achieve complete remission. In this study, we extensively examined the immune dynamics in eight R/R cHL patients treated with CBT, consisting of four complete responders (CR) and four experiencing disease progression (PD), by single cell analysis of peripheral blood mononuclear cells (PBMCs). Our unique approach encompassed longitudinal analysis with three time points, providing a comprehensive understanding of the evolving immune responses during anti-PD1 therapy. Through gene expression profiling, we identified a stable and distinctive KLRG1+/FOS+/JUN+/GZMA+/CD8+ T cell phenotype in patients achieving complete responses. This specific CD8+ T cell subset exhibited sustained activation, underscoring its potential pivotal role in mounting an effective immune response against cHL. Furthermore, T cell receptor (TCR) analysis revealed that in responder patients there is clonal expansion between TCR clonotypes specifically in the KLRG1+/FOS+/JUN+/GZMA+/CD8+ T cell subset. Our longitudinal study offers unique insights into the complex immune dynamics of multiply relapsed/highly pre-treated cHL patients undergoing anti-PD1 therapy.https://www.frontiersin.org/articles/10.3389/fonc.2025.1518107/fullHodgkin (cHL)single-cell analysisTCR - T cell receptorimmunotherapyrefractoriness |
| spellingShingle | Vanessa Cristaldi Lodovico Terzi di Bergamo Lodovico Terzi di Bergamo Lucrezia Patruno Marinos Kallikourdis Marinos Kallikourdis Giada Andrea Cassanmagnago Francesco Corrado Eleonora Calabretta Adalgisa Condoluci Adalgisa Condoluci Martina di Trani Daoud Rahal Gianluca Basso Clelia Peano Alex Graudenzi Alex Graudenzi Marco Antoniotti Marco Antoniotti Davide Rossi Davide Rossi Carmelo Carlo-Stella Carmelo Carlo-Stella The immune cell dynamics in the peripheral blood of cHL patients receiving anti-PD1 treatment Frontiers in Oncology Hodgkin (cHL) single-cell analysis TCR - T cell receptor immunotherapy refractoriness |
| title | The immune cell dynamics in the peripheral blood of cHL patients receiving anti-PD1 treatment |
| title_full | The immune cell dynamics in the peripheral blood of cHL patients receiving anti-PD1 treatment |
| title_fullStr | The immune cell dynamics in the peripheral blood of cHL patients receiving anti-PD1 treatment |
| title_full_unstemmed | The immune cell dynamics in the peripheral blood of cHL patients receiving anti-PD1 treatment |
| title_short | The immune cell dynamics in the peripheral blood of cHL patients receiving anti-PD1 treatment |
| title_sort | immune cell dynamics in the peripheral blood of chl patients receiving anti pd1 treatment |
| topic | Hodgkin (cHL) single-cell analysis TCR - T cell receptor immunotherapy refractoriness |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2025.1518107/full |
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