Selective Internal Radiotherapy Changes the Immune Profiles of Extracellular Vesicles and Their Immune Origin in Patients with Inoperable Cholangiocarcinoma
The incidence of cholangiocellular carcinoma (CCA) is rising worldwide. As there are no specific early symptoms or specific markers of CCA, it is often diagnosed in later inoperable stages. Accumulating evidence underlines the importance of radiation therapy in the induction of antitumor immunity. T...
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MDPI AG
2022-07-01
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| author | Florian Haag Anjana Manikkam Daniel Kraft Caroline Bär Vanessa Wilke Aleksander J. Nowak Jessica Bertrand Jazan Omari Maciej Pech Severin Gylstorff Borna Relja |
| author_facet | Florian Haag Anjana Manikkam Daniel Kraft Caroline Bär Vanessa Wilke Aleksander J. Nowak Jessica Bertrand Jazan Omari Maciej Pech Severin Gylstorff Borna Relja |
| author_sort | Florian Haag |
| collection | DOAJ |
| description | The incidence of cholangiocellular carcinoma (CCA) is rising worldwide. As there are no specific early symptoms or specific markers of CCA, it is often diagnosed in later inoperable stages. Accumulating evidence underlines the importance of radiation therapy in the induction of antitumor immunity. The surface protein composition on extracellular vesicles (EVs) relates to originating cells and thus may play a role in vesicle function. We assessed immune profiles of EVs and their immune origin in patients with inoperable CCA prior and after selective internal radiotherapy (SIRT). A total of 47 CCA patients receiving SIRT and 12 healthy volunteers (HV) were included. Blood was withdrawn before therapy (pre T) and after T. EVs were purified from plasma by cluster of differentiation (CD)9-, CD63-, and CD81-immunobead isolation. To detect differently abundant surface markers, dynamic range and EVs input quality were assessed. A total of 37 EVs surface markers were measured by flow cytometry and correlated either with the administered activity dose (MBq) or with the interval until death (month). EVs phenotyping identified lymphocytes, B cells, NK cells, platelets, endothelial cells, leukocyte activation, B cell activation, T and B cell adhesion markers, stem/progenitor cells, and antigen-presenting cells (APC) as EVs-parenteral cells. CD4 and CD8 significantly declined, while other markers significantly increased in CCA patients pre T vs. HV. Platelets-deriving EVs significantly decreased, normalizing to levels of HV but still significantly increasing vs. HV post SIRT. B cells-deriving EVs significantly increased pre T vs. HV, positively correlating with administered activity dose. MHCII and CD40 EVs significantly increased pre SIRT and negatively correlated with administered activity dose, while EVs from antigen presenting cells and CD49e pre SIRT positively correlated with survival time after therapy. Increased levels of CD24 and CD44 in cancer pre T were significantly decreased post T. Among the heterogeneity of EVs that was demonstrated, in particular, B cells-deriving, MHCII, and CD40 positive or APC-deriving EVs need to be further studied for their diagnostic or prognostic relevance in clinical scenarios. |
| first_indexed | 2024-03-09T05:31:35Z |
| format | Article |
| id | doaj.art-ae2f9301352c4b5db95e97145d5a69ac |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T05:31:35Z |
| publishDate | 2022-07-01 |
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| series | Cells |
| spelling | doaj.art-ae2f9301352c4b5db95e97145d5a69ac2023-12-03T12:32:03ZengMDPI AGCells2073-44092022-07-011115230910.3390/cells11152309Selective Internal Radiotherapy Changes the Immune Profiles of Extracellular Vesicles and Their Immune Origin in Patients with Inoperable CholangiocarcinomaFlorian Haag0Anjana Manikkam1Daniel Kraft2Caroline Bär3Vanessa Wilke4Aleksander J. Nowak5Jessica Bertrand6Jazan Omari7Maciej Pech8Severin Gylstorff9Borna Relja10Experimental Radiology, Department of Radiology and Nuclear Medicine, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, GermanyExperimental Radiology, Department of Radiology and Nuclear Medicine, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, GermanyExperimental Radiology, Department of Radiology and Nuclear Medicine, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, GermanyExperimental Radiology, Department of Radiology and Nuclear Medicine, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, GermanyExperimental Radiology, Department of Radiology and Nuclear Medicine, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, GermanyExperimental Radiology, Department of Radiology and Nuclear Medicine, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, GermanyDepartment of Orthopaedic Surgery, Otto-von-Guericke University, 39120 Magdeburg, GermanyExperimental Radiology, Department of Radiology and Nuclear Medicine, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, GermanyExperimental Radiology, Department of Radiology and Nuclear Medicine, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, GermanyExperimental Radiology, Department of Radiology and Nuclear Medicine, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, GermanyExperimental Radiology, Department of Radiology and Nuclear Medicine, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, GermanyThe incidence of cholangiocellular carcinoma (CCA) is rising worldwide. As there are no specific early symptoms or specific markers of CCA, it is often diagnosed in later inoperable stages. Accumulating evidence underlines the importance of radiation therapy in the induction of antitumor immunity. The surface protein composition on extracellular vesicles (EVs) relates to originating cells and thus may play a role in vesicle function. We assessed immune profiles of EVs and their immune origin in patients with inoperable CCA prior and after selective internal radiotherapy (SIRT). A total of 47 CCA patients receiving SIRT and 12 healthy volunteers (HV) were included. Blood was withdrawn before therapy (pre T) and after T. EVs were purified from plasma by cluster of differentiation (CD)9-, CD63-, and CD81-immunobead isolation. To detect differently abundant surface markers, dynamic range and EVs input quality were assessed. A total of 37 EVs surface markers were measured by flow cytometry and correlated either with the administered activity dose (MBq) or with the interval until death (month). EVs phenotyping identified lymphocytes, B cells, NK cells, platelets, endothelial cells, leukocyte activation, B cell activation, T and B cell adhesion markers, stem/progenitor cells, and antigen-presenting cells (APC) as EVs-parenteral cells. CD4 and CD8 significantly declined, while other markers significantly increased in CCA patients pre T vs. HV. Platelets-deriving EVs significantly decreased, normalizing to levels of HV but still significantly increasing vs. HV post SIRT. B cells-deriving EVs significantly increased pre T vs. HV, positively correlating with administered activity dose. MHCII and CD40 EVs significantly increased pre SIRT and negatively correlated with administered activity dose, while EVs from antigen presenting cells and CD49e pre SIRT positively correlated with survival time after therapy. Increased levels of CD24 and CD44 in cancer pre T were significantly decreased post T. Among the heterogeneity of EVs that was demonstrated, in particular, B cells-deriving, MHCII, and CD40 positive or APC-deriving EVs need to be further studied for their diagnostic or prognostic relevance in clinical scenarios.https://www.mdpi.com/2073-4409/11/15/2309CCAEVsbiomarkerMHCdiagnosisprognosis |
| spellingShingle | Florian Haag Anjana Manikkam Daniel Kraft Caroline Bär Vanessa Wilke Aleksander J. Nowak Jessica Bertrand Jazan Omari Maciej Pech Severin Gylstorff Borna Relja Selective Internal Radiotherapy Changes the Immune Profiles of Extracellular Vesicles and Their Immune Origin in Patients with Inoperable Cholangiocarcinoma Cells CCA EVs biomarker MHC diagnosis prognosis |
| title | Selective Internal Radiotherapy Changes the Immune Profiles of Extracellular Vesicles and Their Immune Origin in Patients with Inoperable Cholangiocarcinoma |
| title_full | Selective Internal Radiotherapy Changes the Immune Profiles of Extracellular Vesicles and Their Immune Origin in Patients with Inoperable Cholangiocarcinoma |
| title_fullStr | Selective Internal Radiotherapy Changes the Immune Profiles of Extracellular Vesicles and Their Immune Origin in Patients with Inoperable Cholangiocarcinoma |
| title_full_unstemmed | Selective Internal Radiotherapy Changes the Immune Profiles of Extracellular Vesicles and Their Immune Origin in Patients with Inoperable Cholangiocarcinoma |
| title_short | Selective Internal Radiotherapy Changes the Immune Profiles of Extracellular Vesicles and Their Immune Origin in Patients with Inoperable Cholangiocarcinoma |
| title_sort | selective internal radiotherapy changes the immune profiles of extracellular vesicles and their immune origin in patients with inoperable cholangiocarcinoma |
| topic | CCA EVs biomarker MHC diagnosis prognosis |
| url | https://www.mdpi.com/2073-4409/11/15/2309 |
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