Selective Internal Radiotherapy Alters the Profiles of Systemic Extracellular Vesicles in Hepatocellular Carcinoma
Incidence of hepatocellular carcinoma (HCC) is increasing globally. Radioembolization (RE)/selective internal radiotherapy (SIRT) is a promising treatment for inoperable HCC. RE triggers an immune response, involving extracellular vesicles (EVs) which are crucial for cell communication and tumor dev...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-08-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/15/12512 |
| _version_ | 1797586586095845376 |
|---|---|
| author | Severin Gylstorff Vanessa Wilke Daniel Kraft Jessica Bertrand Maciej Pech Florian Haag Borna Relja |
| author_facet | Severin Gylstorff Vanessa Wilke Daniel Kraft Jessica Bertrand Maciej Pech Florian Haag Borna Relja |
| author_sort | Severin Gylstorff |
| collection | DOAJ |
| description | Incidence of hepatocellular carcinoma (HCC) is increasing globally. Radioembolization (RE)/selective internal radiotherapy (SIRT) is a promising treatment for inoperable HCC. RE triggers an immune response, involving extracellular vesicles (EVs) which are crucial for cell communication and tumor development. This study explores EV immune profiles and origins in patients with inoperable HCC before and after SIRT/RE. Blood samples from 50 HCC-patients treated with SIRT/RE were collected before and after therapy to determine cytokines and isolate EVs using size exclusion chromatography. The dynamic range and EV quality required for detecting variations in surface markers were assessed. Thirty-seven EV surface markers were analyzed using flow cytometry and correlated with clinical parameters. Several immunological markers (CD4, CD2, CD40, CD45, CD49e, CD69, CD209-EVs) were present in the circulation of HCC patients. These markers positively correlated with therapy response and survival. Conversely, B cell CD20, endothelial cell CD146, platelet CD49e, and CD41b EV markers negatively correlated with 60-day survival. Elevated levels of IL-6 and IL-8 before therapy correlated negatively with patient survival, coinciding with a positive correlation with CD20-positive EVs. Plasma EVs from HCC patients exhibit immunological, cancer, and coagulation markers, including potential biomarkers (CD4, CD20, CD49e, CD146). These may enhance our understanding of cancer biology and facilitate SIRT therapy monitoring. |
| first_indexed | 2024-03-11T00:24:09Z |
| format | Article |
| id | doaj.art-2844ebdfa647433dad271cd6e77eebb4 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T00:24:09Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2844ebdfa647433dad271cd6e77eebb42023-11-18T23:06:04ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124151251210.3390/ijms241512512Selective Internal Radiotherapy Alters the Profiles of Systemic Extracellular Vesicles in Hepatocellular CarcinomaSeverin Gylstorff0Vanessa Wilke1Daniel Kraft2Jessica Bertrand3Maciej Pech4Florian Haag5Borna Relja6Experimental Radiology, Department of Radiology and Nuclear Medicine, Otto-von-Guericke-University, 39120 Magdeburg, GermanyExperimental Radiology, Department of Radiology and Nuclear Medicine, Otto-von-Guericke-University, 39120 Magdeburg, GermanyExperimental Radiology, Department of Radiology and Nuclear Medicine, Otto-von-Guericke-University, 39120 Magdeburg, GermanyDepartment of Orthopaedic Surgery, Otto-von-Guericke-University, 39120 Magdeburg, GermanyExperimental Radiology, Department of Radiology and Nuclear Medicine, Otto-von-Guericke-University, 39120 Magdeburg, GermanyExperimental Radiology, Department of Radiology and Nuclear Medicine, Otto-von-Guericke-University, 39120 Magdeburg, GermanyExperimental Radiology, Department of Radiology and Nuclear Medicine, Otto-von-Guericke-University, 39120 Magdeburg, GermanyIncidence of hepatocellular carcinoma (HCC) is increasing globally. Radioembolization (RE)/selective internal radiotherapy (SIRT) is a promising treatment for inoperable HCC. RE triggers an immune response, involving extracellular vesicles (EVs) which are crucial for cell communication and tumor development. This study explores EV immune profiles and origins in patients with inoperable HCC before and after SIRT/RE. Blood samples from 50 HCC-patients treated with SIRT/RE were collected before and after therapy to determine cytokines and isolate EVs using size exclusion chromatography. The dynamic range and EV quality required for detecting variations in surface markers were assessed. Thirty-seven EV surface markers were analyzed using flow cytometry and correlated with clinical parameters. Several immunological markers (CD4, CD2, CD40, CD45, CD49e, CD69, CD209-EVs) were present in the circulation of HCC patients. These markers positively correlated with therapy response and survival. Conversely, B cell CD20, endothelial cell CD146, platelet CD49e, and CD41b EV markers negatively correlated with 60-day survival. Elevated levels of IL-6 and IL-8 before therapy correlated negatively with patient survival, coinciding with a positive correlation with CD20-positive EVs. Plasma EVs from HCC patients exhibit immunological, cancer, and coagulation markers, including potential biomarkers (CD4, CD20, CD49e, CD146). These may enhance our understanding of cancer biology and facilitate SIRT therapy monitoring.https://www.mdpi.com/1422-0067/24/15/12512cancerHCCEVbiomarkerdiagnosisprognosis |
| spellingShingle | Severin Gylstorff Vanessa Wilke Daniel Kraft Jessica Bertrand Maciej Pech Florian Haag Borna Relja Selective Internal Radiotherapy Alters the Profiles of Systemic Extracellular Vesicles in Hepatocellular Carcinoma International Journal of Molecular Sciences cancer HCC EV biomarker diagnosis prognosis |
| title | Selective Internal Radiotherapy Alters the Profiles of Systemic Extracellular Vesicles in Hepatocellular Carcinoma |
| title_full | Selective Internal Radiotherapy Alters the Profiles of Systemic Extracellular Vesicles in Hepatocellular Carcinoma |
| title_fullStr | Selective Internal Radiotherapy Alters the Profiles of Systemic Extracellular Vesicles in Hepatocellular Carcinoma |
| title_full_unstemmed | Selective Internal Radiotherapy Alters the Profiles of Systemic Extracellular Vesicles in Hepatocellular Carcinoma |
| title_short | Selective Internal Radiotherapy Alters the Profiles of Systemic Extracellular Vesicles in Hepatocellular Carcinoma |
| title_sort | selective internal radiotherapy alters the profiles of systemic extracellular vesicles in hepatocellular carcinoma |
| topic | cancer HCC EV biomarker diagnosis prognosis |
| url | https://www.mdpi.com/1422-0067/24/15/12512 |
| work_keys_str_mv | AT severingylstorff selectiveinternalradiotherapyalterstheprofilesofsystemicextracellularvesiclesinhepatocellularcarcinoma AT vanessawilke selectiveinternalradiotherapyalterstheprofilesofsystemicextracellularvesiclesinhepatocellularcarcinoma AT danielkraft selectiveinternalradiotherapyalterstheprofilesofsystemicextracellularvesiclesinhepatocellularcarcinoma AT jessicabertrand selectiveinternalradiotherapyalterstheprofilesofsystemicextracellularvesiclesinhepatocellularcarcinoma AT maciejpech selectiveinternalradiotherapyalterstheprofilesofsystemicextracellularvesiclesinhepatocellularcarcinoma AT florianhaag selectiveinternalradiotherapyalterstheprofilesofsystemicextracellularvesiclesinhepatocellularcarcinoma AT bornarelja selectiveinternalradiotherapyalterstheprofilesofsystemicextracellularvesiclesinhepatocellularcarcinoma |