PMID- 27942918 OWN - NLM STAT- MEDLINE DCOM- 20170414 LR - 20181113 IS - 1433-0350 (Electronic) IS - 0256-7040 (Linking) VI - 33 IP - 3 DP - 2017 Mar TI - Immunological low-dose radiation modulates the pediatric medulloblastoma antigens and enhances antibody-dependent cellular cytotoxicity. PG - 429-436 LID - 10.1007/s00381-016-3305-x [doi] AB - BACKGROUND: Immunotherapy can be an effective treatment for pediatric medulloblastoma (MB) patients. However, major subpopulations do not respond to immunotherapy, due to the lack of antigenic mutations or the immune-evasive properties of MB cells. Clinical observations suggest that radiation therapy (RT) may expand the therapeutic reach of immunotherapy. The aim of the present investigation is to study the effect of low-dose X-ray radiation (LDXR, 1 Gy) on the functional immunological responses of MB cells (DAOY, D283, and D341). METHODS: Induction of MB cell death was examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Production of reactive oxygen species (ROS) was measured by fluorescent probes. Changes in the expression of human leukocyte antigen (HLA) molecules and caspase-3 activities during treatment were analyzed using Western blotting and caspase-3 assay. RESULTS: Western blot analysis demonstrated that LDXR upregulated the expression of HLA class I and HLA II molecules by more than 20% compared with control and high-dose (12 Gy) groups in vitro. Several of these HLA subtypes, such as MAGE C1, CD137, and ICAM-1, have demonstrated upregulation. In addition, LDXR increases ROS production in association with phosphorylation of NF-kappaB and cell surface expression of mAb target molecules (HER2 and VEGF). These data suggest that a combined LDXR and mAb therapy can create a synergistic effect in vitro. CONCLUSION: These results suggest that LDXR modulates HLA molecules, leading to alterations in T-cell/tumor-cell interaction and enhancement of T-cell-mediated MB cell death. Also, low-dose radiotherapy combined with monoclonal antibody therapy may one day augment the standard treatment for MB, but more investigation is needed to prove its utility as a new therapeutic combination for MB patients. FAU - Das, Arabinda AU - Das A AD - Department of Neurosurgery and MUSC Brain and Spine Tumor Program CSB 310, Medical University of South Carolina, Charleston, SC, 29425, USA. dasa@musc.edu. FAU - McDonald, Daniel AU - McDonald D AD - Department of Radiation Oncology, Medical University of South Carolina, Charleston, SC, USA. FAU - Lowe, Stephen AU - Lowe S AD - Department of Neurosurgery and MUSC Brain and Spine Tumor Program CSB 310, Medical University of South Carolina, Charleston, SC, 29425, USA. FAU - Bredlau, Amy-Lee AU - Bredlau AL AD - Department of Neurosurgery and MUSC Brain and Spine Tumor Program CSB 310, Medical University of South Carolina, Charleston, SC, 29425, USA. AD - Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USA. FAU - Vanek, Kenneth AU - Vanek K AD - Department of Radiation Oncology, Medical University of South Carolina, Charleston, SC, USA. FAU - Patel, Sunil J AU - Patel SJ AD - Department of Neurosurgery and MUSC Brain and Spine Tumor Program CSB 310, Medical University of South Carolina, Charleston, SC, 29425, USA. FAU - Cheshier, Samuel AU - Cheshier S AD - Department of Pediatric Neurosurgery Stanford University School of Medicine, Stanford, CA, USA. FAU - Eskandari, Ramin AU - Eskandari R AD - Department of Neurosurgery and MUSC Brain and Spine Tumor Program CSB 310, Medical University of South Carolina, Charleston, SC, 29425, USA. eskandar@musc.edu. AD - Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USA. eskandar@musc.edu. LA - eng PT - Journal Article DEP - 20161209 PL - Germany TA - Childs Nerv Syst JT - Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery JID - 8503227 RN - 0 (4-1BB Ligand) RN - 0 (Antibodies, Monoclonal) RN - 0 (HLA Antigens) RN - 0 (NF-kappa B) RN - 0 (Reactive Oxygen Species) RN - 0 (TNFSF9 protein, human) RN - 0 (Vascular Endothelial Growth Factor A) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - EC 2.7.10.1 (ERBB2 protein, human) RN - EC 2.7.10.1 (Receptor, ErbB-2) RN - EC 3.4.22.- (Caspase 3) SB - IM MH - 4-1BB Ligand/metabolism MH - Analysis of Variance MH - Antibodies, Monoclonal/*pharmacology MH - Caspase 3/metabolism MH - Cell Line, Tumor/*radiation effects MH - Cell Survival/drug effects MH - Dose-Response Relationship, Radiation MH - Gene Expression Regulation, Neoplastic/drug effects/*radiation effects MH - HLA Antigens/immunology/*metabolism MH - Humans MH - Intercellular Adhesion Molecule-1/metabolism MH - Medulloblastoma/*metabolism/pathology MH - NF-kappa B/metabolism MH - *Radiation MH - Reactive Oxygen Species/metabolism MH - Receptor, ErbB-2/immunology MH - Time Factors MH - Vascular Endothelial Growth Factor A/immunology OTO - NOTNLM OT - HLA OT - Immunomodulation OT - Medulloblastoma OT - Radiation OT - mAb EDAT- 2016/12/13 06:00 MHDA- 2017/04/15 06:00 CRDT- 2016/12/13 06:00 PHST- 2016/10/13 00:00 [received] PHST- 2016/11/23 00:00 [accepted] PHST- 2016/12/13 06:00 [pubmed] PHST- 2017/04/15 06:00 [medline] PHST- 2016/12/13 06:00 [entrez] AID - 10.1007/s00381-016-3305-x [pii] AID - 10.1007/s00381-016-3305-x [doi] PST - ppublish SO - Childs Nerv Syst. 2017 Mar;33(3):429-436. doi: 10.1007/s00381-016-3305-x. Epub 2016 Dec 9.