Longitudinal analysis of DC subsets in patients with ovarian cancer: Implications for immunotherapy
BackgroundThe use of circulating cDC1 to generate anti-cancer vaccines is among the most promising approaches to overcome the limited immunogenicity and clinical efficacy of monocyte-derived DC. However, the recurrent lymphopenia and the reduction of DC numbers and functionality in patients with can...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1119371/full |
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| author | Beatris Mastelic-Gavillet Beatris Mastelic-Gavillet Apostolos Sarivalasis Leyder Elena Lozano Leyder Elena Lozano Sebastien Lofek Sebastien Lofek Tania Wyss Tania Wyss Tania Wyss Ignacio Melero Ignacio Melero Ignacio Melero Ignacio Melero I. Jolanda M. de Vries Alexandre Harari Alexandre Harari Pedro Romero Pedro Romero Lana Elias Kandalaft Lana Elias Kandalaft Selena Viganó Selena Viganó |
| author_facet | Beatris Mastelic-Gavillet Beatris Mastelic-Gavillet Apostolos Sarivalasis Leyder Elena Lozano Leyder Elena Lozano Sebastien Lofek Sebastien Lofek Tania Wyss Tania Wyss Tania Wyss Ignacio Melero Ignacio Melero Ignacio Melero Ignacio Melero I. Jolanda M. de Vries Alexandre Harari Alexandre Harari Pedro Romero Pedro Romero Lana Elias Kandalaft Lana Elias Kandalaft Selena Viganó Selena Viganó |
| author_sort | Beatris Mastelic-Gavillet |
| collection | DOAJ |
| description | BackgroundThe use of circulating cDC1 to generate anti-cancer vaccines is among the most promising approaches to overcome the limited immunogenicity and clinical efficacy of monocyte-derived DC. However, the recurrent lymphopenia and the reduction of DC numbers and functionality in patients with cancer may represent an important limitation of such approach. In patients with ovarian cancer (OvC) that had received chemotherapy, we previously showed that cDC1 frequency and function were reduced.MethodsWe recruited healthy donors (HD, n=7) and patients with OvC at diagnosis and undergoing interval debulking surgery (IDS, n=6), primary debulking surgery (PDS, n=6) or at relapse (n=8). We characterized longitudinally phenotypic and functional properties of peripheral DC subsets by multiparametric flow cytometry.ResultsWe show that the frequency of cDC1 and the total CD141+ DC capacity to take up antigen are not reduced at the diagnosis, while their TLR3 responsiveness is partially impaired in comparison with HD. Chemotherapy causes cDC1 depletion and increase in cDC2 frequency, but mainly in patients belonging to the PDS group, while in the IDS group both total lymphocytes and cDC1 are preserved. The capacity of total CD141+ DC and cDC2 to take up antigen is not impacted by chemotherapy, while the activation capacity upon Poly(I:C) (TLR3L) stimulation is further decreased.ConclusionsOur study provides new information about the impact of chemotherapy on the immune system of patients with OvC and sheds a new light on the importance of considering timing with respect to chemotherapy when designing new vaccination strategies that aim at withdrawing or targeting specific DC subsets. |
| first_indexed | 2024-04-10T16:05:54Z |
| format | Article |
| id | doaj.art-5be54e6c692e4311960f34643d9bcf9e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T16:05:54Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-5be54e6c692e4311960f34643d9bcf9e2023-02-10T04:48:41ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-02-011410.3389/fimmu.2023.11193711119371Longitudinal analysis of DC subsets in patients with ovarian cancer: Implications for immunotherapyBeatris Mastelic-Gavillet0Beatris Mastelic-Gavillet1Apostolos Sarivalasis2Leyder Elena Lozano3Leyder Elena Lozano4Sebastien Lofek5Sebastien Lofek6Tania Wyss7Tania Wyss8Tania Wyss9Ignacio Melero10Ignacio Melero11Ignacio Melero12Ignacio Melero13I. Jolanda M. de Vries14Alexandre Harari15Alexandre Harari16Pedro Romero17Pedro Romero18Lana Elias Kandalaft19Lana Elias Kandalaft20Selena Viganó21Selena Viganó22Department of Oncology, Centre Hospitalier Universitaire Vaudois and Lausanne University Hospital, Lausanne, SwitzerlandLudwig Institute for Cancer Research, University of Lausanne, Lausanne, SwitzerlandDepartment of Oncology, Centre Hospitalier Universitaire Vaudois and Lausanne University Hospital, Lausanne, SwitzerlandDepartment of Oncology, Centre Hospitalier Universitaire Vaudois and Lausanne University Hospital, Lausanne, SwitzerlandLudwig Institute for Cancer Research, University of Lausanne, Lausanne, SwitzerlandDepartment of Oncology, Centre Hospitalier Universitaire Vaudois and Lausanne University Hospital, Lausanne, SwitzerlandLudwig Institute for Cancer Research, University of Lausanne, Lausanne, SwitzerlandDepartment of Oncology, Centre Hospitalier Universitaire Vaudois and Lausanne University Hospital, Lausanne, SwitzerlandLudwig Institute for Cancer Research, University of Lausanne, Lausanne, SwitzerlandBioinformatics Core Facility, Swiss Institute of Bioinformatics (SIB), Lausanne, SwitzerlandDivision of Immunology and Immunotherapy, Center for Applied Medical Research, University of Navarra, Pamplona, SpainInstituto de Investigacion Sanitaria de Navarra, Pamplona, SpainDepartments of Immunology-Immunotherapy and Oncology, University Clinic, University of Navarra, Pamplona, SpainProgram of Immunology and Immunotherapy, Centro de Investigacion Biomedica en Red Cancer, Madrid, SpainDepartment of Tumour Immunology, Radboud Institute of Molecular Life Sciences, Nijmegen, NetherlandsDepartment of Oncology, Centre Hospitalier Universitaire Vaudois and Lausanne University Hospital, Lausanne, SwitzerlandLudwig Institute for Cancer Research, University of Lausanne, Lausanne, SwitzerlandDepartment of Oncology, Centre Hospitalier Universitaire Vaudois and Lausanne University Hospital, Lausanne, SwitzerlandLudwig Institute for Cancer Research, University of Lausanne, Lausanne, SwitzerlandDepartment of Oncology, Centre Hospitalier Universitaire Vaudois and Lausanne University Hospital, Lausanne, SwitzerlandLudwig Institute for Cancer Research, University of Lausanne, Lausanne, SwitzerlandDepartment of Oncology, Centre Hospitalier Universitaire Vaudois and Lausanne University Hospital, Lausanne, SwitzerlandLudwig Institute for Cancer Research, University of Lausanne, Lausanne, SwitzerlandBackgroundThe use of circulating cDC1 to generate anti-cancer vaccines is among the most promising approaches to overcome the limited immunogenicity and clinical efficacy of monocyte-derived DC. However, the recurrent lymphopenia and the reduction of DC numbers and functionality in patients with cancer may represent an important limitation of such approach. In patients with ovarian cancer (OvC) that had received chemotherapy, we previously showed that cDC1 frequency and function were reduced.MethodsWe recruited healthy donors (HD, n=7) and patients with OvC at diagnosis and undergoing interval debulking surgery (IDS, n=6), primary debulking surgery (PDS, n=6) or at relapse (n=8). We characterized longitudinally phenotypic and functional properties of peripheral DC subsets by multiparametric flow cytometry.ResultsWe show that the frequency of cDC1 and the total CD141+ DC capacity to take up antigen are not reduced at the diagnosis, while their TLR3 responsiveness is partially impaired in comparison with HD. Chemotherapy causes cDC1 depletion and increase in cDC2 frequency, but mainly in patients belonging to the PDS group, while in the IDS group both total lymphocytes and cDC1 are preserved. The capacity of total CD141+ DC and cDC2 to take up antigen is not impacted by chemotherapy, while the activation capacity upon Poly(I:C) (TLR3L) stimulation is further decreased.ConclusionsOur study provides new information about the impact of chemotherapy on the immune system of patients with OvC and sheds a new light on the importance of considering timing with respect to chemotherapy when designing new vaccination strategies that aim at withdrawing or targeting specific DC subsets.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1119371/fullDCovarian cancercancer vaccineTLR3chemotherapy |
| spellingShingle | Beatris Mastelic-Gavillet Beatris Mastelic-Gavillet Apostolos Sarivalasis Leyder Elena Lozano Leyder Elena Lozano Sebastien Lofek Sebastien Lofek Tania Wyss Tania Wyss Tania Wyss Ignacio Melero Ignacio Melero Ignacio Melero Ignacio Melero I. Jolanda M. de Vries Alexandre Harari Alexandre Harari Pedro Romero Pedro Romero Lana Elias Kandalaft Lana Elias Kandalaft Selena Viganó Selena Viganó Longitudinal analysis of DC subsets in patients with ovarian cancer: Implications for immunotherapy Frontiers in Immunology DC ovarian cancer cancer vaccine TLR3 chemotherapy |
| title | Longitudinal analysis of DC subsets in patients with ovarian cancer: Implications for immunotherapy |
| title_full | Longitudinal analysis of DC subsets in patients with ovarian cancer: Implications for immunotherapy |
| title_fullStr | Longitudinal analysis of DC subsets in patients with ovarian cancer: Implications for immunotherapy |
| title_full_unstemmed | Longitudinal analysis of DC subsets in patients with ovarian cancer: Implications for immunotherapy |
| title_short | Longitudinal analysis of DC subsets in patients with ovarian cancer: Implications for immunotherapy |
| title_sort | longitudinal analysis of dc subsets in patients with ovarian cancer implications for immunotherapy |
| topic | DC ovarian cancer cancer vaccine TLR3 chemotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1119371/full |
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