Abstract

Carbon ion radiation is a promising treatment for brain cancer; however, the immune system involved long-term systemic effects evoke a concern of complementary and alternative therapies in clinical treatment. To clarify radiotherapy caused fundamental changes in peripheral immune system, examinations were performed based on established models in vitro and in vivo. We found that brain-localized carbon ion radiation of neural cells induced complex changes in the peripheral blood, thymus, and spleen at one, two, and three months after its application. Atrophy, apoptosis, and abnormal T-cell distributions were observed in rats receiving a single high dose of radiation. Radiation downregulated the expression of proteins involved in T-cell development at the transcriptional level and increased the proportion of CD3+CD4−CD8+ T-cells in the thymus and the proportion of CD3+CD4+CD8− T-cells in the spleen. These data show that brain irradiation severely affects the peripheral immune system, even at relatively long times after irradiation. In addition, they provide valuable information that will implement the design of biological-based strategies that will aid brain cancer patients suffering from the long-term side effects of radiation.

Highlights

  • Owing to the physical properties of carbon ion beams, carbon ion radiotherapy is preferentially recommended for treatment of brain cancers [1,2]

  • We examined the long-term effects on the peripheral immune system, including the peripheral blood, thymus, and spleen, after neural cell injury caused by carbon ion radiation in vitro and in vivo

  • Medium conditioned by neural cells receiving 5 Gy of radiation increased the viability of both THP-1 and Jurkat cells compared with medium conditioned by mock-irradiated neural cells (Figure 1A,B)

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Summary

Introduction

Owing to the physical properties of carbon ion beams, carbon ion radiotherapy is preferentially recommended for treatment of brain cancers [1,2]. Previous studies focused on acute responses [24,25,26], despite the persistence of systemic effects modulated by immune system usually last for several or more months after treatment completion [27,28]. This focus may reflect the difficulty of assessing long-term responses owing to the emergence of complex defense mechanisms over time or the overemphasis on acute side effects that cause physical damage. We examined the long-term effects on the peripheral immune system, including the peripheral blood, thymus, and spleen, after neural cell injury caused by carbon ion radiation in vitro and in vivo

Carbon Ion-Irradiated Neural Cells Mediate Immune Effects in Vitro
Carbon Ion-Irradiated Neural Cells Mediate Immune Effects in Vivo
Discussion
Cells and Animals
Carbon Ion Radiation Procedure and Experimental Design
Histopathology and Apoptosis
Real-Time Quantitative PCR
Flow Cytometry Analysis of T Lymphocyte Subsets
Complete Blood Count of Peripheral Blood
Cell Viability Assay
Cell Migration Assays
4.10. Statistical Analysis
Full Text
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