Immunophenotyping of Circulating and Intratumoral Myeloid and T Cells in Glioblastoma Patients
Glioblastoma is the most common and lethal primary brain malignancy that almost inevitably recurs as therapy-refractory cancer. While the success of immune checkpoint blockade (ICB) revealed the immense potential of immune-targeted therapies in several types of cancers outside the central nervous sy...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/23/5751 |
| _version_ | 1797463574296133632 |
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| author | Sascha Marx Fabian Wilken Lea Miebach Mikael Ispirjan Frederik Kinnen Sebastian Paul Sandra Bien-Möller Eric Freund Jörg Baldauf Steffen Fleck Nikolai Siebert Holger Lode Andreas Stahl Bernhard H. Rauch Stephan Singer Christoph Ritter Henry W. S. Schroeder Sander Bekeschus |
| author_facet | Sascha Marx Fabian Wilken Lea Miebach Mikael Ispirjan Frederik Kinnen Sebastian Paul Sandra Bien-Möller Eric Freund Jörg Baldauf Steffen Fleck Nikolai Siebert Holger Lode Andreas Stahl Bernhard H. Rauch Stephan Singer Christoph Ritter Henry W. S. Schroeder Sander Bekeschus |
| author_sort | Sascha Marx |
| collection | DOAJ |
| description | Glioblastoma is the most common and lethal primary brain malignancy that almost inevitably recurs as therapy-refractory cancer. While the success of immune checkpoint blockade (ICB) revealed the immense potential of immune-targeted therapies in several types of cancers outside the central nervous system, it failed to show objective responses in glioblastoma patients as of now. The ability of glioblastoma cells to drive multiple modes of T cell dysfunction while exhibiting low-quality neoepitopes, low-mutational load, and poor antigen priming limits anti-tumor immunity and efficacy of antigen-unspecific immunotherapies such as ICB. An in-depth understanding of the GBM immune landscape is essential to delineate and reprogram such immunosuppressive circuits during disease progression. In this view, the present study aimed to characterize the peripheral and intratumoral immune compartments of 35 glioblastoma patients compared to age- and sex-matched healthy control probands, particularly focusing on exhaustion signatures on myeloid and T cell subsets. Compared to healthy control participants, different immune signatures were already found in the peripheral circulation, partially related to the steroid medication the patients received. Intratumoral CD4+ and CD8+ TEM cells (CD62L<sup>low</sup>/CD45RO<sup>high</sup>) revealed a high expression of PD1, which was also increased on intratumoral, pro-tumorigenic macrophages/microglia. Histopathological analysis further identified high PSGL-1 expression levels of the latter, which has recently been linked to increased metastasis in melanoma and colon cancer via P-selectin-mediated platelet activation. Overall, the present study comprises immunophenotyping of a patient cohort to give implications for eligible immunotherapeutic targets in neurooncology in the future. |
| first_indexed | 2024-03-09T17:52:41Z |
| format | Article |
| id | doaj.art-c4585cf8061142b0a2311d247e33ea3c |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T17:52:41Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-c4585cf8061142b0a2311d247e33ea3c2023-11-24T10:38:03ZengMDPI AGCancers2072-66942022-11-011423575110.3390/cancers14235751Immunophenotyping of Circulating and Intratumoral Myeloid and T Cells in Glioblastoma PatientsSascha Marx0Fabian Wilken1Lea Miebach2Mikael Ispirjan3Frederik Kinnen4Sebastian Paul5Sandra Bien-Möller6Eric Freund7Jörg Baldauf8Steffen Fleck9Nikolai Siebert10Holger Lode11Andreas Stahl12Bernhard H. Rauch13Stephan Singer14Christoph Ritter15Henry W. S. Schroeder16Sander Bekeschus17Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215, USADepartment of Neurosurgery, Greifswald University Medical Center, Ferdinand-Sauerbruch-Str., 17475 Greifswald, GermanyZIK <i>plasmatis</i>, Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Str. 2, 17489 Greifswald, GermanyDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215, USADepartment of Neurosurgery, Greifswald University Medical Center, Ferdinand-Sauerbruch-Str., 17475 Greifswald, GermanyDepartment of Ophthalmology, Greifswald University Medical Center, Ferdinand-Sauerbruch-Str., 17475 Greifswald, GermanyDepartment of Neurosurgery, Greifswald University Medical Center, Ferdinand-Sauerbruch-Str., 17475 Greifswald, GermanyZIK <i>plasmatis</i>, Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Str. 2, 17489 Greifswald, GermanyDepartment of Neurosurgery, Greifswald University Medical Center, Ferdinand-Sauerbruch-Str., 17475 Greifswald, GermanyDepartment of Neurosurgery, Greifswald University Medical Center, Ferdinand-Sauerbruch-Str., 17475 Greifswald, GermanyDepartment of Pediatric Oncology, Greifswald University Medical Center, Ferdinand-Sauerbruch-Str., 17475 Greifswald, GermanyDepartment of Pediatric Oncology, Greifswald University Medical Center, Ferdinand-Sauerbruch-Str., 17475 Greifswald, GermanyDepartment of Ophthalmology, Greifswald University Medical Center, Ferdinand-Sauerbruch-Str., 17475 Greifswald, GermanyPharmacology and Toxicology, Department of Human Medicine, University of Oldenburg, Carl-von-Ossietzky-Str. 9-11, 26129 Oldenburg, GermanyDepartment of Pathology, Greifswald University Medical Center, Ferdinand-Sauerbruch-Str., 17475 Greifswald, GermanyInstitute of Clinical Pharmacy, Greifswald University, Felix-Hausdorff-Str. 3, 17489 Greifswald, GermanyDepartment of Neurosurgery, Greifswald University Medical Center, Ferdinand-Sauerbruch-Str., 17475 Greifswald, GermanyZIK <i>plasmatis</i>, Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Str. 2, 17489 Greifswald, GermanyGlioblastoma is the most common and lethal primary brain malignancy that almost inevitably recurs as therapy-refractory cancer. While the success of immune checkpoint blockade (ICB) revealed the immense potential of immune-targeted therapies in several types of cancers outside the central nervous system, it failed to show objective responses in glioblastoma patients as of now. The ability of glioblastoma cells to drive multiple modes of T cell dysfunction while exhibiting low-quality neoepitopes, low-mutational load, and poor antigen priming limits anti-tumor immunity and efficacy of antigen-unspecific immunotherapies such as ICB. An in-depth understanding of the GBM immune landscape is essential to delineate and reprogram such immunosuppressive circuits during disease progression. In this view, the present study aimed to characterize the peripheral and intratumoral immune compartments of 35 glioblastoma patients compared to age- and sex-matched healthy control probands, particularly focusing on exhaustion signatures on myeloid and T cell subsets. Compared to healthy control participants, different immune signatures were already found in the peripheral circulation, partially related to the steroid medication the patients received. Intratumoral CD4+ and CD8+ TEM cells (CD62L<sup>low</sup>/CD45RO<sup>high</sup>) revealed a high expression of PD1, which was also increased on intratumoral, pro-tumorigenic macrophages/microglia. Histopathological analysis further identified high PSGL-1 expression levels of the latter, which has recently been linked to increased metastasis in melanoma and colon cancer via P-selectin-mediated platelet activation. Overall, the present study comprises immunophenotyping of a patient cohort to give implications for eligible immunotherapeutic targets in neurooncology in the future.https://www.mdpi.com/2072-6694/14/23/5751CD163GBMgliomamacrophagesPD1PSGL-1 |
| spellingShingle | Sascha Marx Fabian Wilken Lea Miebach Mikael Ispirjan Frederik Kinnen Sebastian Paul Sandra Bien-Möller Eric Freund Jörg Baldauf Steffen Fleck Nikolai Siebert Holger Lode Andreas Stahl Bernhard H. Rauch Stephan Singer Christoph Ritter Henry W. S. Schroeder Sander Bekeschus Immunophenotyping of Circulating and Intratumoral Myeloid and T Cells in Glioblastoma Patients Cancers CD163 GBM glioma macrophages PD1 PSGL-1 |
| title | Immunophenotyping of Circulating and Intratumoral Myeloid and T Cells in Glioblastoma Patients |
| title_full | Immunophenotyping of Circulating and Intratumoral Myeloid and T Cells in Glioblastoma Patients |
| title_fullStr | Immunophenotyping of Circulating and Intratumoral Myeloid and T Cells in Glioblastoma Patients |
| title_full_unstemmed | Immunophenotyping of Circulating and Intratumoral Myeloid and T Cells in Glioblastoma Patients |
| title_short | Immunophenotyping of Circulating and Intratumoral Myeloid and T Cells in Glioblastoma Patients |
| title_sort | immunophenotyping of circulating and intratumoral myeloid and t cells in glioblastoma patients |
| topic | CD163 GBM glioma macrophages PD1 PSGL-1 |
| url | https://www.mdpi.com/2072-6694/14/23/5751 |
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