Abstract
Low-dose irradiation (LDI) has recently been shown to have various beneficial effects on human health, such as on cellular metabolic activities, DNA repair, antioxidant activity, homeostasis potency, and immune activation. Although studies on the immunogenic effects of LDI are rapidly accumulating, clinical trials for cancer treatment are considered premature owing to the lack of available preclinical results and protocols. Here, we aim to investigate anti-tumor and anti-metastatic effects of whole-body LDI in several tumor-bearing mouse models. Mice were exposed to single or fractionated whole-body LDI prior to tumor transplantation, and tumor growth and metastatic potential were determined, along with analysis of immune cell populations and expression of epithelial–mesenchymal transition (EMT) markers. Whole-body fractionated-LDI decreased tumor development and lung metastasis not only by infiltration of CD4+, CD8+ T-cells, and dendritic cells (DCs) but also by attenuating EMT. Moreover, a combination of whole-body LDI with localized high-dose radiation therapy reduced the non-irradiated abscopal tumor growth and increased infiltration of effector T cells and DCs. Therefore, whole-body LDI in combination with high-dose radiation therapy could be a potential therapeutic strategy for treating cancer.
Highlights
According to many studies on the biological effects of low-dose irradiation (LDI), defined as doses less than 100 mGy, Low-dose irradiation (LDI) has been shown to induce beneficial effects from bacteria to humans through diverse cellular changes, including adaptive responses, bystander effects, genomic instability, and coordinated response [1,2,3,4]
Given the previous findings on the effect of LDI on anti-tumor and immunomodulatory activity, we initially examined the effect of whole-body LDI in experimental models of lung metastasis
To examine whether whole-body LDI alters the characteristics of tumor cells, B16F10 whole-body LDI alters the characteristics of tumor cells, B16F10 cells from lungs were isolated, and the cells from lungs were isolated, and the proliferative activity was measured
Summary
According to many studies on the biological effects of low-dose irradiation (LDI), defined as doses less than 100 mGy, LDI has been shown to induce beneficial effects from bacteria to humans through diverse cellular changes, including adaptive responses, bystander effects, genomic instability, and coordinated response [1,2,3,4]. These observations cannot be explained by the linear-no-threshold hypothesis, which is adopted to establish radiation protection guidelines to define how health risks increase linearly based on the radiation dose without a threshold [5]. RT to local tumors can generate and release tumor-associated neoantigens, resulting in the elicitation of antigen-specific T cells and a significant reduction in systemic tumor burden in a CD8+ T-cell-dependent fashion [13,14,15,16]
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