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Changes in Peripheral Blood Regulatory T Cells and IL-6 and IL-10 Levels Predict Response of Pediatric Medulloblastoma and Germ Cell Tumors With Residual or Disseminated Disease to Craniospinal Irradiation.

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Title: Changes in Peripheral Blood Regulatory T Cells and IL-6 and IL-10 Levels Predict Response of Pediatric Medulloblastoma and Germ Cell Tumors With Residual or Disseminated Disease to Craniospinal Irradiation.
Authors: Song, Linan1,2 (AUTHOR), Wang, Shuo1 (AUTHOR), Fang, Tong2 (AUTHOR), Qiu, Xiaoguang3 (AUTHOR), Wang, Xiaoli1 (AUTHOR), Zhou, Xinna1 (AUTHOR), Morse, Michael A.4 (AUTHOR), Hobeika, Amy4 (AUTHOR), Wu, Wanshui5 (AUTHOR), Yang, Huabing1 (AUTHOR), Ren, Jun1,4 (AUTHOR) jun.ren@duke.edu, Lyerly, Herbert Kim1,4 (AUTHOR) kim.lyerly@duke.edu
Source: International Journal of Radiation Oncology, Biology, Physics. Oct2021, Vol. 111 Issue 2, p479-490. 12p.
Subjects: Regulatory T cells, Germ cell tumors, Brain tumors, Central nervous system tumors, Lymphocyte subsets, Suppressor cells, T cells, Interleukins, Research, Research methodology, Gliomas, Evaluation research, Comparative studies, Logistic regression analysis, Central nervous system
Abstract: Purpose: Radiation therapy (RT) modulates immune cells and cytokines, resulting in both clinically beneficial and detrimental effects. The changes in peripheral blood T lymphocyte subsets and cytokines during RT for pediatric brain tumors and the association of these changes with therapeutic outcomes have not been well described.Methods and Materials: The study population consisted of children (n = 83, aged 3~18) with primary brain tumors (medulloblastoma, glioma, germ cell tumors (GCT), and central nervous system embryonal tumor-not otherwise specified), with or without residual or disseminated (R/D) diseases who were starting standard postoperative focal or craniospinal irradiation (CSI). Peripheral blood T lymphocyte subsets collected before and 4 weeks after RT were enumerated by flow cytometry. Plasma levels of interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-α, interferon-γ, and IL-17A were measured by cytometric bead array.Results: Patients with R/D lesions receiving CSI (n = 32) had a post-RT increase in the frequency of CD3+T and CD8+T cells, a decrease in CD4+T cells, and an increase in regulatory T cells (Tregs) and CD8+CD28- suppressor cells, which was more predominantly seen in these patients than in other groups. In the CSI group with such R/D lesions, consisting of patients with medulloblastoma and germ cell tumors, 19 experienced a complete response (CR) and 13 experienced a partial response (PR) on imaging at 4 weeks after RT. The post/pre-RT ratio of Tregs (P = .0493), IL-6 (P = .0111), and IL-10 (P = .0070) was lower in the CR group than in the PR group. Multivariate analysis revealed that the post/pre-RT ratios of Treg, IL-6, and IL-10 were independent predictors of CR (P < .0001, P = .018, P < .0001, respectively). The areas under the receiver operating curves and confidence intervals were 0.7652 (0.5831-0.8964), 0.7794 (0.5980-0.9067), and 0.7085 (0.5223-0.8552) for IL-6, IL-10, and Treg, respectively. The sensitivities of IL-6, IL-10, and Treg to predict radiotherapeutic responses were 100%, 92.3%, and 61.5%, and specificity was 52.6%, 57.9%, and 84.2%, respectively.Conclusions: CSI treatment to those with R/D lesions predominantly exerted an effect on antitumor immune response compared with both R/D lesion-free but exposed to focal or CSI RT and with R/D lesions and exposed to focal RT. Such CSI with R/D lesions group experiencing CR is more likely to have a decrease in immunoinhibitory molecules and cells than patients who only achieve PR. Measuring peripheral blood Treg, IL-6, and IL-10 levels could be valuable for predicting radiotherapeutic responses of pediatric brain tumors with R/D lesions to CSI for medulloblastoma and intracranial germ cell tumors. [ABSTRACT FROM AUTHOR]
Copyright of International Journal of Radiation Oncology, Biology, Physics is the property of Pergamon Press - An Imprint of Elsevier Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Changes in Peripheral Blood Regulatory T Cells and IL-6 and IL-10 Levels Predict Response of Pediatric Medulloblastoma and Germ Cell Tumors With Residual or Disseminated Disease to Craniospinal Irradiation.
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  Data: &lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Song%2C+Linan%22&quot;&gt;Song, Linan&lt;/searchLink&gt;&lt;relatesTo&gt;1,2&lt;/relatesTo&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Wang%2C+Shuo%22&quot;&gt;Wang, Shuo&lt;/searchLink&gt;&lt;relatesTo&gt;1&lt;/relatesTo&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Fang%2C+Tong%22&quot;&gt;Fang, Tong&lt;/searchLink&gt;&lt;relatesTo&gt;2&lt;/relatesTo&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Qiu%2C+Xiaoguang%22&quot;&gt;Qiu, Xiaoguang&lt;/searchLink&gt;&lt;relatesTo&gt;3&lt;/relatesTo&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Wang%2C+Xiaoli%22&quot;&gt;Wang, Xiaoli&lt;/searchLink&gt;&lt;relatesTo&gt;1&lt;/relatesTo&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Zhou%2C+Xinna%22&quot;&gt;Zhou, Xinna&lt;/searchLink&gt;&lt;relatesTo&gt;1&lt;/relatesTo&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Morse%2C+Michael+A%2E%22&quot;&gt;Morse, Michael A.&lt;/searchLink&gt;&lt;relatesTo&gt;4&lt;/relatesTo&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Hobeika%2C+Amy%22&quot;&gt;Hobeika, Amy&lt;/searchLink&gt;&lt;relatesTo&gt;4&lt;/relatesTo&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Wu%2C+Wanshui%22&quot;&gt;Wu, Wanshui&lt;/searchLink&gt;&lt;relatesTo&gt;5&lt;/relatesTo&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Yang%2C+Huabing%22&quot;&gt;Yang, Huabing&lt;/searchLink&gt;&lt;relatesTo&gt;1&lt;/relatesTo&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Ren%2C+Jun%22&quot;&gt;Ren, Jun&lt;/searchLink&gt;&lt;relatesTo&gt;1,4&lt;/relatesTo&gt; (AUTHOR)&lt;i&gt; jun.ren@duke.edu&lt;/i&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Lyerly%2C+Herbert+Kim%22&quot;&gt;Lyerly, Herbert Kim&lt;/searchLink&gt;&lt;relatesTo&gt;1,4&lt;/relatesTo&gt; (AUTHOR)&lt;i&gt; kim.lyerly@duke.edu&lt;/i&gt;
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  Data: &lt;searchLink fieldCode=&quot;JN&quot; term=&quot;%22International+Journal+of+Radiation+Oncology%2C+Biology%2C+Physics%22&quot;&gt;International Journal of Radiation Oncology, Biology, Physics&lt;/searchLink&gt;. Oct2021, Vol. 111 Issue 2, p479-490. 12p.
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– Name: Abstract
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  Data: &lt;bold&gt;Purpose: &lt;/bold&gt;Radiation therapy (RT) modulates immune cells and cytokines, resulting in both clinically beneficial and detrimental effects. The changes in peripheral blood T lymphocyte subsets and cytokines during RT for pediatric brain tumors and the association of these changes with therapeutic outcomes have not been well described.&lt;bold&gt;Methods and Materials: &lt;/bold&gt;The study population consisted of children (n&#160;=&#160;83, aged 3~18) with primary brain tumors (medulloblastoma, glioma, germ cell tumors (GCT), and central nervous system embryonal tumor-not otherwise specified), with or without residual or disseminated (R/D) diseases who were starting standard postoperative focal or craniospinal irradiation (CSI). Peripheral blood T lymphocyte subsets collected before and 4 weeks after RT were enumerated by flow cytometry. Plasma levels of interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-α, interferon-γ, and IL-17A were measured by cytometric bead array.&lt;bold&gt;Results: &lt;/bold&gt;Patients with R/D lesions receiving CSI (n&#160;=&#160;32) had a post-RT increase in the frequency of CD3+T and CD8+T cells, a decrease in CD4+T cells, and an increase in regulatory T cells (Tregs) and CD8+CD28- suppressor cells, which was more predominantly seen in these patients than in other groups. In the CSI group with such R/D lesions, consisting of patients with medulloblastoma and germ cell tumors, 19 experienced a complete response (CR) and 13 experienced a partial response (PR) on imaging at 4 weeks after RT. The post/pre-RT ratio of Tregs (P&#160;=&#160;.0493), IL-6 (P&#160;=&#160;.0111), and IL-10 (P&#160;=&#160;.0070) was lower in the CR group than in the PR group. Multivariate analysis revealed that the post/pre-RT ratios of Treg, IL-6, and IL-10 were independent predictors of CR (P &lt; .0001, P&#160;=&#160;.018, P &lt; .0001, respectively). The areas under the receiver operating curves and confidence intervals were 0.7652 (0.5831-0.8964), 0.7794 (0.5980-0.9067), and 0.7085 (0.5223-0.8552) for IL-6, IL-10, and Treg, respectively. The sensitivities of IL-6, IL-10, and Treg to predict radiotherapeutic responses were 100%, 92.3%, and 61.5%, and specificity was 52.6%, 57.9%, and 84.2%, respectively.&lt;bold&gt;Conclusions: &lt;/bold&gt;CSI treatment to those with R/D lesions predominantly exerted an effect on antitumor immune response compared with both R/D lesion-free but exposed to focal or CSI RT and with R/D lesions and exposed to focal RT. Such CSI with R/D lesions group experiencing CR is more likely to have a decrease in immunoinhibitory molecules and cells than patients who only achieve PR. Measuring peripheral blood Treg, IL-6, and IL-10 levels could be valuable for predicting radiotherapeutic responses of pediatric brain tumors with R/D lesions to CSI for medulloblastoma and intracranial germ cell tumors. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
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  Data: &lt;i&gt;Copyright of International Journal of Radiation Oncology, Biology, Physics is the property of Pergamon Press - An Imprint of Elsevier Science and its content may not be copied or emailed to multiple sites without the copyright holder&#39;s express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.&lt;/i&gt; (Copyright applies to all Abstracts.)
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        Value: 10.1016/j.ijrobp.2021.04.041
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        Text: English
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    Subjects:
      – SubjectFull: Regulatory T cells
        Type: general
      – SubjectFull: Germ cell tumors
        Type: general
      – SubjectFull: Brain tumors
        Type: general
      – SubjectFull: Central nervous system tumors
        Type: general
      – SubjectFull: Lymphocyte subsets
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      – SubjectFull: Suppressor cells
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      – SubjectFull: T cells
        Type: general
      – SubjectFull: Interleukins
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      – SubjectFull: Research
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      – SubjectFull: Research methodology
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      – SubjectFull: Gliomas
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      – SubjectFull: Evaluation research
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      – SubjectFull: Comparative studies
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      – SubjectFull: Central nervous system
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    Titles:
      – TitleFull: Changes in Peripheral Blood Regulatory T Cells and IL-6 and IL-10 Levels Predict Response of Pediatric Medulloblastoma and Germ Cell Tumors With Residual or Disseminated Disease to Craniospinal Irradiation.
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              Text: Oct2021
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