Autologous Dendritic Cell Therapy in Mesothelioma Patients Enhances Frequencies of Peripheral CD4 T Cells Expressing HLA-DR, PD-1, or ICOS
Introduction: Malignant pleural mesothelioma (MPM) is a malignancy with a very poor prognosis for which new treatment options are urgently needed. We have previously shown that dendritic cell (DC) immunotherapy provides a clinically feasible treatment option. In the current study, we set out to asse...
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Frontiers Media S.A.
2018-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.02034/full |
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| author | Pauline L. de Goeje Pauline L. de Goeje Yarne Klaver Yarne Klaver Margaretha E. H. Kaijen-Lambers Margaretha E. H. Kaijen-Lambers Anton W. Langerak Heleen Vroman Heleen Vroman André Kunert André Kunert André Kunert Cor H. J. Lamers Cor H. J. Lamers Joachim G. J. V. Aerts Joachim G. J. V. Aerts Reno Debets Reno Debets Rudi W. Hendriks |
| author_facet | Pauline L. de Goeje Pauline L. de Goeje Yarne Klaver Yarne Klaver Margaretha E. H. Kaijen-Lambers Margaretha E. H. Kaijen-Lambers Anton W. Langerak Heleen Vroman Heleen Vroman André Kunert André Kunert André Kunert Cor H. J. Lamers Cor H. J. Lamers Joachim G. J. V. Aerts Joachim G. J. V. Aerts Reno Debets Reno Debets Rudi W. Hendriks |
| author_sort | Pauline L. de Goeje |
| collection | DOAJ |
| description | Introduction: Malignant pleural mesothelioma (MPM) is a malignancy with a very poor prognosis for which new treatment options are urgently needed. We have previously shown that dendritic cell (DC) immunotherapy provides a clinically feasible treatment option. In the current study, we set out to assess the immunological changes induced by DC immunotherapy in peripheral blood of MPM patients.Methods: Peripheral blood was collected from nine patients enrolled in a phase I dose escalation study, before and after treatment with DCs that were pulsed with an allogeneic tumor lysate preparation consisting of a mixture of five cultured mesothelioma cell lines. We used immune profiling by multiplex flow cytometry to characterize different populations of immune cells. In particular, we determined frequencies of T cell subsets that showed single and combinatorial expression of multiple markers that signify T cell activation, maturation and inhibition. Therapy-induced T cell reactivity was assessed in peptide/MHC multimer stainings using mesothelin as a prototypic target antigen with confirmed expression in the clinical tumor lysate preparation. T cell receptor (TCR) diversity was evaluated by TCRB gene PCR assays.Results: We observed an increase in the numbers of B cells, CD4 and CD8 T cells, but not NK cells at 6 weeks post-treatment. The increases in B and T lymphocytes were not accompanied by major changes in T cell reactivity toward mesothelin nor in TCRB diversity. Notably, we did observe enhanced proportions of CD4 T cells expressing HLA-DR, PD-1 (at 2 weeks after onset of treatment) and ICOS (6 weeks) and a CD8 T cell population expressing LAG3 (2 weeks).Discussion: DC immunotherapy using allogeneic tumor lysate resulted in enhanced frequencies of B cells and T cells in blood. We did not detect a skewed antigen-reactivity of peripheral CD8 T cells. Interestingly, frequencies of CD4 T cells expressing activation markers and PD-1 were increased. These findings indicate a systemic activation of the adaptive immune response and may guide future immune monitoring studies of DC therapies. |
| first_indexed | 2024-12-11T17:27:06Z |
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| language | English |
| last_indexed | 2024-12-11T17:27:06Z |
| publishDate | 2018-09-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-36ed6879f3464311bdefb121712c13062022-12-22T00:56:57ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-09-01910.3389/fimmu.2018.02034376160Autologous Dendritic Cell Therapy in Mesothelioma Patients Enhances Frequencies of Peripheral CD4 T Cells Expressing HLA-DR, PD-1, or ICOSPauline L. de Goeje0Pauline L. de Goeje1Yarne Klaver2Yarne Klaver3Margaretha E. H. Kaijen-Lambers4Margaretha E. H. Kaijen-Lambers5Anton W. Langerak6Heleen Vroman7Heleen Vroman8André Kunert9André Kunert10André Kunert11Cor H. J. Lamers12Cor H. J. Lamers13Joachim G. J. V. Aerts14Joachim G. J. V. Aerts15Reno Debets16Reno Debets17Rudi W. Hendriks18Department of Pulmonary Medicine, Erasmus MC, Rotterdam, NetherlandsErasmus MC Cancer Institute, Erasmus MC, Rotterdam, NetherlandsErasmus MC Cancer Institute, Erasmus MC, Rotterdam, NetherlandsDepartment of Medical Oncology, Laboratory of Tumor Immunology, Erasmus MC, Rotterdam, NetherlandsDepartment of Pulmonary Medicine, Erasmus MC, Rotterdam, NetherlandsErasmus MC Cancer Institute, Erasmus MC, Rotterdam, NetherlandsDepartment of Immunology, Laboratory Medical Immunology, Erasmus MC, Rotterdam, NetherlandsDepartment of Pulmonary Medicine, Erasmus MC, Rotterdam, NetherlandsErasmus MC Cancer Institute, Erasmus MC, Rotterdam, NetherlandsDepartment of Pulmonary Medicine, Erasmus MC, Rotterdam, NetherlandsErasmus MC Cancer Institute, Erasmus MC, Rotterdam, NetherlandsDepartment of Medical Oncology, Laboratory of Tumor Immunology, Erasmus MC, Rotterdam, NetherlandsErasmus MC Cancer Institute, Erasmus MC, Rotterdam, NetherlandsDepartment of Medical Oncology, Laboratory of Tumor Immunology, Erasmus MC, Rotterdam, NetherlandsDepartment of Pulmonary Medicine, Erasmus MC, Rotterdam, NetherlandsErasmus MC Cancer Institute, Erasmus MC, Rotterdam, NetherlandsErasmus MC Cancer Institute, Erasmus MC, Rotterdam, NetherlandsDepartment of Medical Oncology, Laboratory of Tumor Immunology, Erasmus MC, Rotterdam, NetherlandsDepartment of Pulmonary Medicine, Erasmus MC, Rotterdam, NetherlandsIntroduction: Malignant pleural mesothelioma (MPM) is a malignancy with a very poor prognosis for which new treatment options are urgently needed. We have previously shown that dendritic cell (DC) immunotherapy provides a clinically feasible treatment option. In the current study, we set out to assess the immunological changes induced by DC immunotherapy in peripheral blood of MPM patients.Methods: Peripheral blood was collected from nine patients enrolled in a phase I dose escalation study, before and after treatment with DCs that were pulsed with an allogeneic tumor lysate preparation consisting of a mixture of five cultured mesothelioma cell lines. We used immune profiling by multiplex flow cytometry to characterize different populations of immune cells. In particular, we determined frequencies of T cell subsets that showed single and combinatorial expression of multiple markers that signify T cell activation, maturation and inhibition. Therapy-induced T cell reactivity was assessed in peptide/MHC multimer stainings using mesothelin as a prototypic target antigen with confirmed expression in the clinical tumor lysate preparation. T cell receptor (TCR) diversity was evaluated by TCRB gene PCR assays.Results: We observed an increase in the numbers of B cells, CD4 and CD8 T cells, but not NK cells at 6 weeks post-treatment. The increases in B and T lymphocytes were not accompanied by major changes in T cell reactivity toward mesothelin nor in TCRB diversity. Notably, we did observe enhanced proportions of CD4 T cells expressing HLA-DR, PD-1 (at 2 weeks after onset of treatment) and ICOS (6 weeks) and a CD8 T cell population expressing LAG3 (2 weeks).Discussion: DC immunotherapy using allogeneic tumor lysate resulted in enhanced frequencies of B cells and T cells in blood. We did not detect a skewed antigen-reactivity of peripheral CD8 T cells. Interestingly, frequencies of CD4 T cells expressing activation markers and PD-1 were increased. These findings indicate a systemic activation of the adaptive immune response and may guide future immune monitoring studies of DC therapies.https://www.frontiersin.org/article/10.3389/fimmu.2018.02034/fulldendritic cell vaccinationmesotheliomaimmune monitoringT lymphocytesimmunotherapy of cancerinducible T-cell co-stimulator protein |
| spellingShingle | Pauline L. de Goeje Pauline L. de Goeje Yarne Klaver Yarne Klaver Margaretha E. H. Kaijen-Lambers Margaretha E. H. Kaijen-Lambers Anton W. Langerak Heleen Vroman Heleen Vroman André Kunert André Kunert André Kunert Cor H. J. Lamers Cor H. J. Lamers Joachim G. J. V. Aerts Joachim G. J. V. Aerts Reno Debets Reno Debets Rudi W. Hendriks Autologous Dendritic Cell Therapy in Mesothelioma Patients Enhances Frequencies of Peripheral CD4 T Cells Expressing HLA-DR, PD-1, or ICOS Frontiers in Immunology dendritic cell vaccination mesothelioma immune monitoring T lymphocytes immunotherapy of cancer inducible T-cell co-stimulator protein |
| title | Autologous Dendritic Cell Therapy in Mesothelioma Patients Enhances Frequencies of Peripheral CD4 T Cells Expressing HLA-DR, PD-1, or ICOS |
| title_full | Autologous Dendritic Cell Therapy in Mesothelioma Patients Enhances Frequencies of Peripheral CD4 T Cells Expressing HLA-DR, PD-1, or ICOS |
| title_fullStr | Autologous Dendritic Cell Therapy in Mesothelioma Patients Enhances Frequencies of Peripheral CD4 T Cells Expressing HLA-DR, PD-1, or ICOS |
| title_full_unstemmed | Autologous Dendritic Cell Therapy in Mesothelioma Patients Enhances Frequencies of Peripheral CD4 T Cells Expressing HLA-DR, PD-1, or ICOS |
| title_short | Autologous Dendritic Cell Therapy in Mesothelioma Patients Enhances Frequencies of Peripheral CD4 T Cells Expressing HLA-DR, PD-1, or ICOS |
| title_sort | autologous dendritic cell therapy in mesothelioma patients enhances frequencies of peripheral cd4 t cells expressing hla dr pd 1 or icos |
| topic | dendritic cell vaccination mesothelioma immune monitoring T lymphocytes immunotherapy of cancer inducible T-cell co-stimulator protein |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.02034/full |
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