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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
- Source :
- International Journal of Radiation Oncology*Biology*Physics. 111:479-490
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- 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.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.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.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.
- Subjects :
- Male
Cancer Research
Pathology
medicine.medical_specialty
Adolescent
medicine.medical_treatment
T-Lymphocytes, Regulatory
030218 nuclear medicine & medical imaging
03 medical and health sciences
0302 clinical medicine
Immune system
Craniospinal Irradiation
T-Lymphocyte Subsets
Glioma
medicine
Humans
Radiology, Nuclear Medicine and imaging
Cerebellar Neoplasms
Child
Medulloblastoma
Radiation
Interleukin-6
business.industry
CD28
Neoplasms, Germ Cell and Embryonal
medicine.disease
Interleukin-10
Interleukin 10
Logistic Models
Cytokine
Oncology
Child, Preschool
030220 oncology & carcinogenesis
Female
Germ cell tumors
business
CD8
Subjects
Details
- ISSN :
- 03603016
- Volume :
- 111
- Database :
- OpenAIRE
- Journal :
- International Journal of Radiation Oncology*Biology*Physics
- Accession number :
- edsair.doi.dedup.....f76fef2817750830206e82b9a5e43235