Sustained Accumulation of Blood-Derived Macrophages in the Immune Microenvironment of Patients with Recurrent Glioblastoma after Therapy
The cell composition of the glioblastoma (GBM) microenvironment depends on the recruitment of myeloid cells from the blood, promoting tumor progression by inducing immunosuppression. This phenomenon hampers immunotherapies and investigating its complexity may help to tailor new treatments. Periphera...
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MDPI AG
2021-12-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/24/6178 |
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| author | Sara Magri Beatrice Musca Camilla Bonaudo Ada Tushe Maria Giovanna Russo Elena Masetto Vittorina Zagonel Giuseppe Lombardi Alessandro Della Puppa Susanna Mandruzzato |
| author_facet | Sara Magri Beatrice Musca Camilla Bonaudo Ada Tushe Maria Giovanna Russo Elena Masetto Vittorina Zagonel Giuseppe Lombardi Alessandro Della Puppa Susanna Mandruzzato |
| author_sort | Sara Magri |
| collection | DOAJ |
| description | The cell composition of the glioblastoma (GBM) microenvironment depends on the recruitment of myeloid cells from the blood, promoting tumor progression by inducing immunosuppression. This phenomenon hampers immunotherapies and investigating its complexity may help to tailor new treatments. Peripheral blood and tissue specimens from the central and marginal tumor areas were collected from 44 primary and 19 recurrent GBM patients. Myeloid and lymphoid cell subsets and the levels of immunosuppressive markers were defined by multiparametric flow cytometry. Multiplexed immunohistochemistry was used to confirm the differences in the immune infiltrate and to analyze the cell spatial distribution. Relapsing GBM showed an increased presence of blood-derived macrophages in both tumor areas and a higher frequency of infiltrating lymphocytes, with a high level of exhaustion markers. The expansion of some myeloid-derived suppressor cell (MDSC) subsets in the blood was found in both primary and recurrent GBM patients. A significant inverse correlation between infiltrating T cells and an MDSC subset was also found. In patients with recurrent GBM after standard first-line therapy, the immune-hostile tumor microenvironment and the levels of some MDSC subsets in the blood persisted. Analysis of the immune landscape in GBM relapses aids in the definition of more appropriate stratification and treatment. |
| first_indexed | 2024-03-10T04:32:17Z |
| format | Article |
| id | doaj.art-f0f517e4ff724c7b82ec274b05a028ae |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T04:32:17Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-f0f517e4ff724c7b82ec274b05a028ae2023-11-23T04:04:49ZengMDPI AGCancers2072-66942021-12-011324617810.3390/cancers13246178Sustained Accumulation of Blood-Derived Macrophages in the Immune Microenvironment of Patients with Recurrent Glioblastoma after TherapySara Magri0Beatrice Musca1Camilla Bonaudo2Ada Tushe3Maria Giovanna Russo4Elena Masetto5Vittorina Zagonel6Giuseppe Lombardi7Alessandro Della Puppa8Susanna Mandruzzato9Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, ItalyImmunology and Molecular Oncology, Veneto Institute of Oncology IOV—IRCCS, 35128 Padova, ItalyNeurosurgery, Department of NEUROFARBA, University Hospital of Careggi, University of Florence, 50134 Florence, ItalyDepartment of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, ItalyImmunology and Molecular Oncology, Veneto Institute of Oncology IOV—IRCCS, 35128 Padova, ItalyImmunology and Molecular Oncology, Veneto Institute of Oncology IOV—IRCCS, 35128 Padova, ItalyMedical Oncology Unit 1, Veneto Institute of Oncology IOV—IRCCS, 35128 Padova, ItalyMedical Oncology Unit 1, Veneto Institute of Oncology IOV—IRCCS, 35128 Padova, ItalyNeurosurgery, Department of NEUROFARBA, University Hospital of Careggi, University of Florence, 50134 Florence, ItalyDepartment of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, ItalyThe cell composition of the glioblastoma (GBM) microenvironment depends on the recruitment of myeloid cells from the blood, promoting tumor progression by inducing immunosuppression. This phenomenon hampers immunotherapies and investigating its complexity may help to tailor new treatments. Peripheral blood and tissue specimens from the central and marginal tumor areas were collected from 44 primary and 19 recurrent GBM patients. Myeloid and lymphoid cell subsets and the levels of immunosuppressive markers were defined by multiparametric flow cytometry. Multiplexed immunohistochemistry was used to confirm the differences in the immune infiltrate and to analyze the cell spatial distribution. Relapsing GBM showed an increased presence of blood-derived macrophages in both tumor areas and a higher frequency of infiltrating lymphocytes, with a high level of exhaustion markers. The expansion of some myeloid-derived suppressor cell (MDSC) subsets in the blood was found in both primary and recurrent GBM patients. A significant inverse correlation between infiltrating T cells and an MDSC subset was also found. In patients with recurrent GBM after standard first-line therapy, the immune-hostile tumor microenvironment and the levels of some MDSC subsets in the blood persisted. Analysis of the immune landscape in GBM relapses aids in the definition of more appropriate stratification and treatment.https://www.mdpi.com/2072-6694/13/24/6178glioblastomamacrophagestumor microenvironmentrecurrence/relapse |
| spellingShingle | Sara Magri Beatrice Musca Camilla Bonaudo Ada Tushe Maria Giovanna Russo Elena Masetto Vittorina Zagonel Giuseppe Lombardi Alessandro Della Puppa Susanna Mandruzzato Sustained Accumulation of Blood-Derived Macrophages in the Immune Microenvironment of Patients with Recurrent Glioblastoma after Therapy Cancers glioblastoma macrophages tumor microenvironment recurrence/relapse |
| title | Sustained Accumulation of Blood-Derived Macrophages in the Immune Microenvironment of Patients with Recurrent Glioblastoma after Therapy |
| title_full | Sustained Accumulation of Blood-Derived Macrophages in the Immune Microenvironment of Patients with Recurrent Glioblastoma after Therapy |
| title_fullStr | Sustained Accumulation of Blood-Derived Macrophages in the Immune Microenvironment of Patients with Recurrent Glioblastoma after Therapy |
| title_full_unstemmed | Sustained Accumulation of Blood-Derived Macrophages in the Immune Microenvironment of Patients with Recurrent Glioblastoma after Therapy |
| title_short | Sustained Accumulation of Blood-Derived Macrophages in the Immune Microenvironment of Patients with Recurrent Glioblastoma after Therapy |
| title_sort | sustained accumulation of blood derived macrophages in the immune microenvironment of patients with recurrent glioblastoma after therapy |
| topic | glioblastoma macrophages tumor microenvironment recurrence/relapse |
| url | https://www.mdpi.com/2072-6694/13/24/6178 |
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