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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.
Song, Linan; Wang, Shuo; Fang, Tong; Qiu, Xiaoguang; Wang, Xiaoli; Zhou, Xinna; Morse, Michael A; Hobeika, Amy; Wu, Wanshui; Yang, Huabing; Ren, Jun; Lyerly, Herbert Kim.
Afiliação
  • Song L; Departments of Medical Oncology, Beijing Key Laboratory for Therapeutic Cancer Vaccines, Capital Medical University Cancer Center, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China; Departments of Radio-Oncology, Capital Medical University Cancer Center, Beijing Shijitan H
  • Wang S; Departments of Medical Oncology, Beijing Key Laboratory for Therapeutic Cancer Vaccines, Capital Medical University Cancer Center, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.
  • Fang T; Departments of Radio-Oncology, Capital Medical University Cancer Center, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.
  • Qiu X; Department of Radiotherapy, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
  • Wang X; Departments of Medical Oncology, Beijing Key Laboratory for Therapeutic Cancer Vaccines, Capital Medical University Cancer Center, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.
  • Zhou X; Departments of Medical Oncology, Beijing Key Laboratory for Therapeutic Cancer Vaccines, Capital Medical University Cancer Center, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.
  • Morse MA; Department of Surgery, Duke University Medical Center, Durham, North Carolina.
  • Hobeika A; Department of Surgery, Duke University Medical Center, Durham, North Carolina.
  • Wu W; Department of Pediatrics, Capital Medical University Cancer Center, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.
  • Yang H; Departments of Medical Oncology, Beijing Key Laboratory for Therapeutic Cancer Vaccines, Capital Medical University Cancer Center, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.
  • Ren J; Departments of Medical Oncology, Beijing Key Laboratory for Therapeutic Cancer Vaccines, Capital Medical University Cancer Center, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China; Department of Surgery, Duke University Medical Center, Durham, North Carolina. Electronic a
  • Lyerly HK; Department of Surgery, Duke University Medical Center, Durham, North Carolina. Electronic address: kim.lyerly@duke.edu.
Int J Radiat Oncol Biol Phys ; 111(2): 479-490, 2021 10 01.
Article em En | MEDLINE | ID: mdl-33974888
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Cerebelares / Interleucina-6 / Interleucina-10 / Linfócitos T Reguladores / Neoplasias Embrionárias de Células Germinativas / Radiação Cranioespinal / Meduloblastoma Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Adolescent / Child / Child, preschool / Female / Humans / Male Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Cerebelares / Interleucina-6 / Interleucina-10 / Linfócitos T Reguladores / Neoplasias Embrionárias de Células Germinativas / Radiação Cranioespinal / Meduloblastoma Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Adolescent / Child / Child, preschool / Female / Humans / Male Idioma: En Ano de publicação: 2021 Tipo de documento: Article