Gamma knife radiosurgery compared to whole brain radiation therapy enhances immunity via immunoregulatory molecules in patients with metastatic brain tumours

Background: There is lack of data on the effect of stereotactic radiosurgery in modulation of the immune system for cancer patients with metastatic brain tumours. Therefore, we investigated the change in levels of immunoregulatory molecules after Gamma Knife radiosurgery (GKR) and whole brain radiat...

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Published in:British journal of neurosurgery 2020-12, Vol.34 (6), p.604-610
Main Authors: Hatiboglu, Mustafa Aziz, Kocyigit, Abdurrahim, Guler, Eray Metin, Nalli, Arife, Akdur, Kerime, Sakarcan, Ayten, Ozek, Erdinc, Uysal, Omer, Mayadagli, Alpaslan
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Language:English
Subjects:
Brain
Brain cancer
Brain Neoplasms - radiotherapy
Brain Neoplasms - surgery
Cytokines
gamma knife radiosurgery
Humans
Immune system
Immunity
Metastasis
radiation
Radiation therapy
Radiosurgery
Retrospective Studies
Tumors
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cited_by cdi_FETCH-LOGICAL-c394t-685a7055004e832ebcea90418a8a7303b7cc1dd2ab637be7904df78ed5971c3b3
cites cdi_FETCH-LOGICAL-c394t-685a7055004e832ebcea90418a8a7303b7cc1dd2ab637be7904df78ed5971c3b3
container_end_page 610
container_issue 6
container_start_page 604
container_title British journal of neurosurgery
container_volume 34
creator Hatiboglu, Mustafa Aziz
Kocyigit, Abdurrahim
Guler, Eray Metin
Nalli, Arife
Akdur, Kerime
Sakarcan, Ayten
Ozek, Erdinc
Uysal, Omer
Mayadagli, Alpaslan
description Background: There is lack of data on the effect of stereotactic radiosurgery in modulation of the immune system for cancer patients with metastatic brain tumours. Therefore, we investigated the change in levels of immunoregulatory molecules after Gamma Knife radiosurgery (GKR) and whole brain radiation therapy (WBRT) in patients with brain metastases. Methods: Peripheral blood samples were collected from 15 patients who received GKR, nine patients who received WBRT for brain metastases and 10 healthy controls. Samples were obtained at three time points such as before, 1h after and 1 week after the index procedure for patients treated with GKR or WBRT. All patients' demographic data and radiosurgical parameters were retrospectively reviewed. We analyzed the change in the levels of T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death ligand-1 (PD-L1), and cytokines such as IL-2, IL-10, IFN-γ, TNF-α after GKR and WBRT using Enzyme-linked immunosorbent assays (ELISA). Results: Baseline level of IFN-γ was found to be lower and that of PD-L1 was higher in the GKR group compared to WBRT group and healthy controls (p 
doi_str_mv 10.1080/02688697.2019.1642445
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Therefore, we investigated the change in levels of immunoregulatory molecules after Gamma Knife radiosurgery (GKR) and whole brain radiation therapy (WBRT) in patients with brain metastases. Methods: Peripheral blood samples were collected from 15 patients who received GKR, nine patients who received WBRT for brain metastases and 10 healthy controls. Samples were obtained at three time points such as before, 1h after and 1 week after the index procedure for patients treated with GKR or WBRT. All patients' demographic data and radiosurgical parameters were retrospectively reviewed. We analyzed the change in the levels of T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death ligand-1 (PD-L1), and cytokines such as IL-2, IL-10, IFN-γ, TNF-α after GKR and WBRT using Enzyme-linked immunosorbent assays (ELISA). Results: Baseline level of IFN-γ was found to be lower and that of PD-L1 was higher in the GKR group compared to WBRT group and healthy controls (p &lt; 0.05 and p &lt; 0.01, respectively). Levels of IFN-γ and IL-2 were increased (p &lt; 0.01 and p &lt; 0.01, respectively), while CTLA-4 and PD-L1 were decreased (p = 0.05 and p = 0.01, respectively) after GKR compared to pre-GKR levels, while there was no change after WBRT. Conclusion: GKR regulates immunoregulatory molecules towards enhancing the immune system, while WBRT did not exert any effect. These findings suggested that treatment of metastatic brain lesion with GKR might stimulate a systemic immune response against the tumour.</description><identifier>ISSN: 0268-8697</identifier><identifier>EISSN: 1360-046X</identifier><identifier>DOI: 10.1080/02688697.2019.1642445</identifier><identifier>PMID: 31317782</identifier><language>eng</language><publisher>England: Taylor &amp; Francis</publisher><subject>Brain ; Brain cancer ; Brain Neoplasms - radiotherapy ; Brain Neoplasms - surgery ; Cytokines ; gamma knife radiosurgery ; Humans ; Immune system ; Immunity ; Metastasis ; radiation ; Radiation therapy ; Radiosurgery ; Retrospective Studies ; Tumors</subject><ispartof>British journal of neurosurgery, 2020-12, Vol.34 (6), p.604-610</ispartof><rights>2019 The Neurosurgical Foundation 2019</rights><rights>2019 The Neurosurgical Foundation</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c394t-685a7055004e832ebcea90418a8a7303b7cc1dd2ab637be7904df78ed5971c3b3</citedby><cites>FETCH-LOGICAL-c394t-685a7055004e832ebcea90418a8a7303b7cc1dd2ab637be7904df78ed5971c3b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31317782$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hatiboglu, Mustafa Aziz</creatorcontrib><creatorcontrib>Kocyigit, Abdurrahim</creatorcontrib><creatorcontrib>Guler, Eray Metin</creatorcontrib><creatorcontrib>Nalli, Arife</creatorcontrib><creatorcontrib>Akdur, Kerime</creatorcontrib><creatorcontrib>Sakarcan, Ayten</creatorcontrib><creatorcontrib>Ozek, Erdinc</creatorcontrib><creatorcontrib>Uysal, Omer</creatorcontrib><creatorcontrib>Mayadagli, Alpaslan</creatorcontrib><title>Gamma knife radiosurgery compared to whole brain radiation therapy enhances immunity via immunoregulatory molecules in patients with metastatic brain tumours</title><title>British journal of neurosurgery</title><addtitle>Br J Neurosurg</addtitle><description>Background: There is lack of data on the effect of stereotactic radiosurgery in modulation of the immune system for cancer patients with metastatic brain tumours. Therefore, we investigated the change in levels of immunoregulatory molecules after Gamma Knife radiosurgery (GKR) and whole brain radiation therapy (WBRT) in patients with brain metastases. Methods: Peripheral blood samples were collected from 15 patients who received GKR, nine patients who received WBRT for brain metastases and 10 healthy controls. Samples were obtained at three time points such as before, 1h after and 1 week after the index procedure for patients treated with GKR or WBRT. All patients' demographic data and radiosurgical parameters were retrospectively reviewed. We analyzed the change in the levels of T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death ligand-1 (PD-L1), and cytokines such as IL-2, IL-10, IFN-γ, TNF-α after GKR and WBRT using Enzyme-linked immunosorbent assays (ELISA). Results: Baseline level of IFN-γ was found to be lower and that of PD-L1 was higher in the GKR group compared to WBRT group and healthy controls (p &lt; 0.05 and p &lt; 0.01, respectively). Levels of IFN-γ and IL-2 were increased (p &lt; 0.01 and p &lt; 0.01, respectively), while CTLA-4 and PD-L1 were decreased (p = 0.05 and p = 0.01, respectively) after GKR compared to pre-GKR levels, while there was no change after WBRT. Conclusion: GKR regulates immunoregulatory molecules towards enhancing the immune system, while WBRT did not exert any effect. These findings suggested that treatment of metastatic brain lesion with GKR might stimulate a systemic immune response against the tumour.</description><subject>Brain</subject><subject>Brain cancer</subject><subject>Brain Neoplasms - radiotherapy</subject><subject>Brain Neoplasms - surgery</subject><subject>Cytokines</subject><subject>gamma knife radiosurgery</subject><subject>Humans</subject><subject>Immune system</subject><subject>Immunity</subject><subject>Metastasis</subject><subject>radiation</subject><subject>Radiation therapy</subject><subject>Radiosurgery</subject><subject>Retrospective Studies</subject><subject>Tumors</subject><issn>0268-8697</issn><issn>1360-046X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9kcFu1DAURS0EokPhE0CWWGew4yR2dqAKWqRKbEBiF704Lx2X2A6201E-hn_F6UxZsrJsn3eu9C4hbznbc6bYB1Y2SjWt3JeMt3veVGVV1c_IjouGFaxqfj4nu40pNuiCvIrxnjFe1ky-JBeCCy6lKnfkzzVYC_SXMyPSAIPxcQl3GFaqvZ0h4ECTp8eDn5D2AYx7hCAZ72g6YIB5pegO4DRGaqxdnEkrfTBwuviAd8sEyWehzQ69TBvn6JwV6FKkR5MO1GKCmPKTPoekxfolxNfkxQhTxDfn85L8-PL5-9VNcfvt-uvVp9tCi7ZKRaNqkKyuGatQiRJ7jdCyiitQIAUTvdSaD0MJfSNkjzL_DaNUONSt5Fr04pK8P3nn4H8vGFN3n-NdjuzKqmkZr4VqMlWfKB18jAHHbg7GQlg7zrqtlO6plG4rpTuXkufene1Lb3H4N_XUQgY-ngDjRh8sHH2Yhi7BOvkwhrxbEzP834y_XuugcA</recordid><startdate>202012</startdate><enddate>202012</enddate><creator>Hatiboglu, Mustafa Aziz</creator><creator>Kocyigit, Abdurrahim</creator><creator>Guler, Eray Metin</creator><creator>Nalli, Arife</creator><creator>Akdur, Kerime</creator><creator>Sakarcan, Ayten</creator><creator>Ozek, Erdinc</creator><creator>Uysal, Omer</creator><creator>Mayadagli, Alpaslan</creator><general>Taylor &amp; Francis</general><general>Taylor &amp; Francis Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope></search><sort><creationdate>202012</creationdate><title>Gamma knife radiosurgery compared to whole brain radiation therapy enhances immunity via immunoregulatory molecules in patients with metastatic brain tumours</title><author>Hatiboglu, Mustafa Aziz ; Kocyigit, Abdurrahim ; Guler, Eray Metin ; Nalli, Arife ; Akdur, Kerime ; Sakarcan, Ayten ; Ozek, Erdinc ; Uysal, Omer ; Mayadagli, Alpaslan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c394t-685a7055004e832ebcea90418a8a7303b7cc1dd2ab637be7904df78ed5971c3b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Brain</topic><topic>Brain cancer</topic><topic>Brain Neoplasms - radiotherapy</topic><topic>Brain Neoplasms - surgery</topic><topic>Cytokines</topic><topic>gamma knife radiosurgery</topic><topic>Humans</topic><topic>Immune system</topic><topic>Immunity</topic><topic>Metastasis</topic><topic>radiation</topic><topic>Radiation therapy</topic><topic>Radiosurgery</topic><topic>Retrospective Studies</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hatiboglu, Mustafa Aziz</creatorcontrib><creatorcontrib>Kocyigit, Abdurrahim</creatorcontrib><creatorcontrib>Guler, Eray Metin</creatorcontrib><creatorcontrib>Nalli, Arife</creatorcontrib><creatorcontrib>Akdur, Kerime</creatorcontrib><creatorcontrib>Sakarcan, Ayten</creatorcontrib><creatorcontrib>Ozek, Erdinc</creatorcontrib><creatorcontrib>Uysal, Omer</creatorcontrib><creatorcontrib>Mayadagli, Alpaslan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><jtitle>British journal of neurosurgery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hatiboglu, Mustafa Aziz</au><au>Kocyigit, Abdurrahim</au><au>Guler, Eray Metin</au><au>Nalli, Arife</au><au>Akdur, Kerime</au><au>Sakarcan, Ayten</au><au>Ozek, Erdinc</au><au>Uysal, Omer</au><au>Mayadagli, Alpaslan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Gamma knife radiosurgery compared to whole brain radiation therapy enhances immunity via immunoregulatory molecules in patients with metastatic brain tumours</atitle><jtitle>British journal of neurosurgery</jtitle><addtitle>Br J Neurosurg</addtitle><date>2020-12</date><risdate>2020</risdate><volume>34</volume><issue>6</issue><spage>604</spage><epage>610</epage><pages>604-610</pages><issn>0268-8697</issn><eissn>1360-046X</eissn><abstract>Background: There is lack of data on the effect of stereotactic radiosurgery in modulation of the immune system for cancer patients with metastatic brain tumours. Therefore, we investigated the change in levels of immunoregulatory molecules after Gamma Knife radiosurgery (GKR) and whole brain radiation therapy (WBRT) in patients with brain metastases. Methods: Peripheral blood samples were collected from 15 patients who received GKR, nine patients who received WBRT for brain metastases and 10 healthy controls. Samples were obtained at three time points such as before, 1h after and 1 week after the index procedure for patients treated with GKR or WBRT. All patients' demographic data and radiosurgical parameters were retrospectively reviewed. We analyzed the change in the levels of T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death ligand-1 (PD-L1), and cytokines such as IL-2, IL-10, IFN-γ, TNF-α after GKR and WBRT using Enzyme-linked immunosorbent assays (ELISA). Results: Baseline level of IFN-γ was found to be lower and that of PD-L1 was higher in the GKR group compared to WBRT group and healthy controls (p &lt; 0.05 and p &lt; 0.01, respectively). Levels of IFN-γ and IL-2 were increased (p &lt; 0.01 and p &lt; 0.01, respectively), while CTLA-4 and PD-L1 were decreased (p = 0.05 and p = 0.01, respectively) after GKR compared to pre-GKR levels, while there was no change after WBRT. Conclusion: GKR regulates immunoregulatory molecules towards enhancing the immune system, while WBRT did not exert any effect. These findings suggested that treatment of metastatic brain lesion with GKR might stimulate a systemic immune response against the tumour.</abstract><cop>England</cop><pub>Taylor &amp; Francis</pub><pmid>31317782</pmid><doi>10.1080/02688697.2019.1642445</doi><tpages>7</tpages></addata></record>
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subjects Brain
Brain cancer
Brain Neoplasms - radiotherapy
Brain Neoplasms - surgery
Cytokines
gamma knife radiosurgery
Humans
Immune system
Immunity
Metastasis
radiation
Radiation therapy
Radiosurgery
Retrospective Studies
Tumors
title Gamma knife radiosurgery compared to whole brain radiation therapy enhances immunity via immunoregulatory molecules in patients with metastatic brain tumours
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