Radiotherapy induces an immediate inflammatory reaction in malignant glioma: a clinical microdialysis study
The knowledge of response to radiation in the immuno-microenvironment of high grade gliomas is sparse. In vitro results have indicated an inflammatory response of myeloid cells after irradiation. Therefore, microdialysis was used to verify whether this is operative in tumor tissue and brain adjacent...
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Published in | Journal of neuro-oncology Vol. 131; no. 1; pp. 83 - 92 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
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Springer US
01.01.2017
Springer Nature B.V |
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Abstract | The knowledge of response to radiation in the immuno-microenvironment of high grade gliomas is sparse. In vitro results have indicated an inflammatory response of myeloid cells after irradiation. Therefore, microdialysis was used to verify whether this is operative in tumor tissue and brain adjacent to tumor (BAT) after clinical radiotherapy of patients with high grade glioma. Stereotactic biopsies and implantation of microdialysis catheters in tumor tissue and BAT were performed in eleven patients with high-grade glioma. The patients were given daily radiation fractions of 2–3.4 Gy. Microdialysis samples were collected before radiotherapy and during the first five days of radiation. Cytokines, glucose metabolites, glutamate and glycerol were analyzed. Immunohistochemistry was performed to detect macrophages (CD68) and monocytes (CD163) as well as IL-6, IL-8 and MCP-1. A significant increase of IL-8, MCP-1 and MIP-1a were detected in tumor tissue already after the first dose of radiation and increased further during 5 days of radiation. IL-6 did also increase but after five fractions of radiation. In BAT, the cytokine response was modest with significant increase of IL-8 after third dose of radiation. We found a positive correlation between baseline IL-8 and IL-6 microdialysis levels in tumor tissue and survival. Glucose metabolites or glycerol and glutamate did not change during radiation. In all tumors staining for macrophages was demonstrated. IL-6 was found in viable tumor cells while MCP-1 was demonstrated in macrophages or tumor matrix. Our findings suggest that radiation induces a rapid enhancement of the prevailing inflammation in high-grade glioma tissue. The microdialysis technique is feasible for this type of study and could be used to monitor metabolic changes after different interventions. |
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AbstractList | The knowledge of response to radiation in the immuno-microenvironment of high grade gliomas is sparse. In vitro results have indicated an inflammatory response of myeloid cells after irradiation. Therefore, microdialysis was used to verify whether this is operative in tumor tissue and brain adjacent to tumor (BAT) after clinical radiotherapy of patients with high grade glioma. Stereotactic biopsies and implantation of microdialysis catheters in tumor tissue and BAT were performed in eleven patients with high-grade glioma. The patients were given daily radiation fractions of 2-3.4 Gy. Microdialysis samples were collected before radiotherapy and during the first five days of radiation. Cytokines, glucose metabolites, glutamate and glycerol were analyzed. Immunohistochemistry was performed to detect macrophages (CD68) and monocytes (CD163) as well as IL-6, IL-8 and MCP-1. A significant increase of IL-8, MCP-1 and MIP-1a were detected in tumor tissue already after the first dose of radiation and increased further during 5 days of radiation. IL-6 did also increase but after five fractions of radiation. In BAT, the cytokine response was modest with significant increase of IL-8 after third dose of radiation. We found a positive correlation between baseline IL-8 and IL-6 microdialysis levels in tumor tissue and survival. Glucose metabolites or glycerol and glutamate did not change during radiation. In all tumors staining for macrophages was demonstrated. IL-6 was found in viable tumor cells while MCP-1 was demonstrated in macrophages or tumor matrix. Our findings suggest that radiation induces a rapid enhancement of the prevailing inflammation in high-grade glioma tissue. The microdialysis technique is feasible for this type of study and could be used to monitor metabolic changes after different interventions. The knowledge of response to radiation in the immuno-microenvironment of high grade gliomas is sparse. In vitro results have indicated an inflammatory response of myeloid cells after irradiation. Therefore, microdialysis was used to verify whether this is operative in tumor tissue and brain adjacent to tumor (BAT) after clinical radiotherapy of patients with high grade glioma. Stereotactic biopsies and implantation of microdialysis catheters in tumor tissue and BAT were performed in eleven patients with high-grade glioma. The patients were given daily radiation fractions of 2–3.4 Gy. Microdialysis samples were collected before radiotherapy and during the first five days of radiation. Cytokines, glucose metabolites, glutamate and glycerol were analyzed. Immunohistochemistry was performed to detect macrophages (CD68) and monocytes (CD163) as well as IL-6, IL-8 and MCP-1. A significant increase of IL-8, MCP-1 and MIP-1a were detected in tumor tissue already after the first dose of radiation and increased further during 5 days of radiation. IL-6 did also increase but after five fractions of radiation. In BAT, the cytokine response was modest with significant increase of IL-8 after third dose of radiation. We found a positive correlation between baseline IL-8 and IL-6 microdialysis levels in tumor tissue and survival. Glucose metabolites or glycerol and glutamate did not change during radiation. In all tumors staining for macrophages was demonstrated. IL-6 was found in viable tumor cells while MCP-1 was demonstrated in macrophages or tumor matrix. Our findings suggest that radiation induces a rapid enhancement of the prevailing inflammation in high-grade glioma tissue. The microdialysis technique is feasible for this type of study and could be used to monitor metabolic changes after different interventions. |
Author | Siesjö, Peter Brännström, Thomas Tabatabaei, Pedram Visse, Eward Bergenheim, A. Tommy Bergström, Per |
Author_xml | – sequence: 1 givenname: Pedram orcidid: 0000-0003-2912-7059 surname: Tabatabaei fullname: Tabatabaei, Pedram email: pedram.tabatabaie@vll.se organization: Department of Clinical Neuroscience, Neurosurgery, Umea University – sequence: 2 givenname: Eward surname: Visse fullname: Visse, Eward organization: Department of Clinical Science, Lund University Hospital – sequence: 3 givenname: Per surname: Bergström fullname: Bergström, Per organization: Department of Radiation Science, Umeå University – sequence: 4 givenname: Thomas surname: Brännström fullname: Brännström, Thomas organization: Department of Medical Bioscience, Umeå University – sequence: 5 givenname: Peter surname: Siesjö fullname: Siesjö, Peter organization: Department of Clinical Science, Lund University Hospital – sequence: 6 givenname: A. Tommy surname: Bergenheim fullname: Bergenheim, A. Tommy organization: Department of Clinical Neuroscience, Neurosurgery, Umea University |
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Keywords | Inflammation Microdialysis Radiotherapy Cytokine Glioblastoma |
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Title | Radiotherapy induces an immediate inflammatory reaction in malignant glioma: a clinical microdialysis study |
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