Longitudinal immune monitoring of patients with resectable esophageal adenocarcinoma treated with Neoadjuvant PD-L1 checkpoint inhibition
The analysis of peripheral blood mononuclear cells (PBMCs) by flow cytometry holds promise as a platform for immune checkpoint inhibition (ICI) biomarker identification. Our aim was to characterize the systemic immune compartment in resectable esophageal adenocarcinoma patients treated with neoadjuv...
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Taylor & Francis Group
2023-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2233403 |
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| author | Tom van den Ende Aiarpi Ezdoglian Lisanne M. Baas Joyce Bakker Sinéad M. Lougheed Micaela Harrasser Cynthia Waasdorp Mark I. van Berge Henegouwen Maarten C.C.M. Hulshof Nadia Haj Mohammad Richard van Hillegersberg Stella Mook Conny J. van der Laken Nicole C.T. van Grieken Sarah Derks Maarten F. Bijlsma Hanneke W.M. van Laarhoven Tanja D. de Gruijl |
| author_facet | Tom van den Ende Aiarpi Ezdoglian Lisanne M. Baas Joyce Bakker Sinéad M. Lougheed Micaela Harrasser Cynthia Waasdorp Mark I. van Berge Henegouwen Maarten C.C.M. Hulshof Nadia Haj Mohammad Richard van Hillegersberg Stella Mook Conny J. van der Laken Nicole C.T. van Grieken Sarah Derks Maarten F. Bijlsma Hanneke W.M. van Laarhoven Tanja D. de Gruijl |
| author_sort | Tom van den Ende |
| collection | DOAJ |
| description | The analysis of peripheral blood mononuclear cells (PBMCs) by flow cytometry holds promise as a platform for immune checkpoint inhibition (ICI) biomarker identification. Our aim was to characterize the systemic immune compartment in resectable esophageal adenocarcinoma patients treated with neoadjuvant ICI therapy. In total, 24 patients treated with neoadjuvant chemoradiotherapy (nCRT) and anti-PD-L1 (atezolizumab) from the PERFECT study (NCT03087864) were included and 26 patients from a previously published nCRT cohort. Blood samples were collected at baseline, on-treatment, before and after surgery. Response groups for comparison were defined as pathological complete responders (pCR) or patients with pathological residual disease (non-pCR). Based on multicolor flow cytometry of PBMCs, an immunosuppressive phenotype was observed in the non-pCR group of the PERFECT cohort, characterized by a higher percentage of regulatory T cells (Tregs), intermediate monocytes, and a lower percentage of type-2 conventional dendritic cells. A further increase in activated Tregs was observed in non-pCR patients on-treatment. These findings were not associated with a poor response in the nCRT cohort. At baseline, immunosuppressive cytokines were elevated in the non-pCR group of the PERFECT study. The suppressive subsets correlated at baseline with a Wnt/β-Catenin gene expression signature and on-treatment with epithelial–mesenchymal transition and angiogenesis signatures from tumor biopsies. After surgery monocyte activation (CD40), low CD8+Ki67+ T cell rates, and the enrichment of CD206+ monocytes were related to early recurrence. These findings highlight systemic barriers to effective ICI and the need for optimized treatment regimens. |
| format | Article |
| id | doaj-art-875b94688d2a4d92a00af551e8bbb88a |
| institution | OA Journals |
| issn | 2162-402X |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-875b94688d2a4d92a00af551e8bbb88a2025-08-20T02:01:30ZengTaylor & Francis GroupOncoImmunology2162-402X2023-12-0112110.1080/2162402X.2023.2233403Longitudinal immune monitoring of patients with resectable esophageal adenocarcinoma treated with Neoadjuvant PD-L1 checkpoint inhibitionTom van den Ende0Aiarpi Ezdoglian1Lisanne M. Baas2Joyce Bakker3Sinéad M. Lougheed4Micaela Harrasser5Cynthia Waasdorp6Mark I. van Berge Henegouwen7Maarten C.C.M. Hulshof8Nadia Haj Mohammad9Richard van Hillegersberg10Stella Mook11Conny J. van der Laken12Nicole C.T. van Grieken13Sarah Derks14Maarten F. Bijlsma15Hanneke W.M. van Laarhoven16Tanja D. de Gruijl17Department of Medical Oncology, Amsterdam UMC, University of Amsterdam, Amsterdam, The NetherlandsDepartment of Medical Oncology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, NetherlandsDepartment of Medical Oncology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, NetherlandsDepartment of Medical Oncology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, NetherlandsDepartment of Medical Oncology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, NetherlandsDepartment of Medical Oncology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, NetherlandsCancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, The NetherlandsDepartment of Surgery, Amsterdam Umc, University of Amsterdam, Amsterdam, The NetherlandsCancer Treatment and Quality of Life, Cancer Center Amsterdam, Amsterdam, The NetherlandsDepartment of Medical Oncology, UMC Utrecht, Utrecht University, Utrecht, The NetherlandsDepartment of Surgery, UMC Utrecht, Utrecht University, Utrecht, The NetherlandsDepartment of Radiotherapy, UMC Utrecht, Utrecht University, Utrecht, The NetherlandsAmsterdam UMC, Vrije Universiteit Amsterdam, Department of Rheumatology and Clinical Immunology, Amsterdam Institute for Infection and Immunity, Amsterdam, The NetherlandsCancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, The NetherlandsDepartment of Medical Oncology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, NetherlandsCancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, The NetherlandsDepartment of Medical Oncology, Amsterdam UMC, University of Amsterdam, Amsterdam, The NetherlandsDepartment of Medical Oncology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, NetherlandsThe analysis of peripheral blood mononuclear cells (PBMCs) by flow cytometry holds promise as a platform for immune checkpoint inhibition (ICI) biomarker identification. Our aim was to characterize the systemic immune compartment in resectable esophageal adenocarcinoma patients treated with neoadjuvant ICI therapy. In total, 24 patients treated with neoadjuvant chemoradiotherapy (nCRT) and anti-PD-L1 (atezolizumab) from the PERFECT study (NCT03087864) were included and 26 patients from a previously published nCRT cohort. Blood samples were collected at baseline, on-treatment, before and after surgery. Response groups for comparison were defined as pathological complete responders (pCR) or patients with pathological residual disease (non-pCR). Based on multicolor flow cytometry of PBMCs, an immunosuppressive phenotype was observed in the non-pCR group of the PERFECT cohort, characterized by a higher percentage of regulatory T cells (Tregs), intermediate monocytes, and a lower percentage of type-2 conventional dendritic cells. A further increase in activated Tregs was observed in non-pCR patients on-treatment. These findings were not associated with a poor response in the nCRT cohort. At baseline, immunosuppressive cytokines were elevated in the non-pCR group of the PERFECT study. The suppressive subsets correlated at baseline with a Wnt/β-Catenin gene expression signature and on-treatment with epithelial–mesenchymal transition and angiogenesis signatures from tumor biopsies. After surgery monocyte activation (CD40), low CD8+Ki67+ T cell rates, and the enrichment of CD206+ monocytes were related to early recurrence. These findings highlight systemic barriers to effective ICI and the need for optimized treatment regimens.https://www.tandfonline.com/doi/10.1080/2162402X.2023.2233403Chemotherapyesophageal neoplasmimmune systemimmunotherapyNeoadjuvant |
| spellingShingle | Tom van den Ende Aiarpi Ezdoglian Lisanne M. Baas Joyce Bakker Sinéad M. Lougheed Micaela Harrasser Cynthia Waasdorp Mark I. van Berge Henegouwen Maarten C.C.M. Hulshof Nadia Haj Mohammad Richard van Hillegersberg Stella Mook Conny J. van der Laken Nicole C.T. van Grieken Sarah Derks Maarten F. Bijlsma Hanneke W.M. van Laarhoven Tanja D. de Gruijl Longitudinal immune monitoring of patients with resectable esophageal adenocarcinoma treated with Neoadjuvant PD-L1 checkpoint inhibition OncoImmunology Chemotherapy esophageal neoplasm immune system immunotherapy Neoadjuvant |
| title | Longitudinal immune monitoring of patients with resectable esophageal adenocarcinoma treated with Neoadjuvant PD-L1 checkpoint inhibition |
| title_full | Longitudinal immune monitoring of patients with resectable esophageal adenocarcinoma treated with Neoadjuvant PD-L1 checkpoint inhibition |
| title_fullStr | Longitudinal immune monitoring of patients with resectable esophageal adenocarcinoma treated with Neoadjuvant PD-L1 checkpoint inhibition |
| title_full_unstemmed | Longitudinal immune monitoring of patients with resectable esophageal adenocarcinoma treated with Neoadjuvant PD-L1 checkpoint inhibition |
| title_short | Longitudinal immune monitoring of patients with resectable esophageal adenocarcinoma treated with Neoadjuvant PD-L1 checkpoint inhibition |
| title_sort | longitudinal immune monitoring of patients with resectable esophageal adenocarcinoma treated with neoadjuvant pd l1 checkpoint inhibition |
| topic | Chemotherapy esophageal neoplasm immune system immunotherapy Neoadjuvant |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2233403 |
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