scholarly journals Evaluation of Anti-Tumor Effects of Whole-Body Low-Dose Irradiation in Metastatic Mouse Models

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1126
Author(s):  
Kyung-Hee Song ◽  
Seung-Youn Jung ◽  
Jeong-In Park ◽  
Jiyeon Ahn ◽  
Jong-Kuk Park ◽  
...  

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.

2020 ◽  
Vol 10 (4) ◽  
pp. e255-e263 ◽  
Author(s):  
Bram D. Vermeulen ◽  
Paul M. Jeene ◽  
Jasmijn Sijben ◽  
Robin Krol ◽  
Heidi Rütten ◽  
...  

2020 ◽  
Vol 9 (3) ◽  
pp. 249-262
Author(s):  
Xiaochang Liu ◽  
Zheng Liu ◽  
Duo Wang ◽  
Yang Han ◽  
Sai Hu ◽  
...  

Abstract Whole-body exposure to low-dose radiation due to diagnostic imaging procedures, occupational hazards and radiation accidents is a source of concern. In this study, we analyzed the effects of single and long-term low-dose irradiation on the immune system. Male Balb/c mice received a single whole-body dose of irradiation (0.01, 0.05, 0.2, 0.5 or 1 Gy). For long-term irradiation, mice were irradiated 10 times (total dose of 0.2, 0.5 or 1 Gy) over a period of 6 weeks. Two days after single or long-term irradiation, the numbers of splenic macrophages, natural killer cells and dendritic cells were reduced, and the spleen organ coefficient was decreased. At 2 Days after long-term low-dose irradiation, the number of white blood cells in the peripheral blood of the mice decreased. Between 7 and 14 Days after long-term low-dose irradiation, the number of immune cells in the thymus and spleen began to increase and then stabilized. Th1/Th2 cytokines and reactive oxygen species-related proteins first decreased and then increased to a plateau. Our results show a significant difference in the effects of single and long-term low-dose irradiation on the immune system.


1981 ◽  
Vol 78 (3) ◽  
pp. 1809-1812 ◽  
Author(s):  
A. F. Tilkin ◽  
N. Schaaf-Lafontaine ◽  
A. Van Acker ◽  
M. Boccadoro ◽  
J. Urbain

2020 ◽  
Vol 8 (2) ◽  
pp. e000537
Author(s):  
Hampartsoum B Barsoumian ◽  
Rishab Ramapriyan ◽  
Ahmed I Younes ◽  
Mauricio S Caetano ◽  
Hari Menon ◽  
...  

BackgroundDespite some successes with checkpoint inhibitors for treating cancer, most patients remain refractory to treatment, possibly due to the inhibitory nature of the tumor stroma that impedes the function and entry of effector cells. We devised a new technique of combining immunotherapy with radiotherapy (XRT), more specifically low-dose XRT, to overcome the stroma and maximize systemic outcomes.MethodsWe bilaterally established 344SQ lung adenocarcinoma tumors in 129Sv/Ev mice. Primary and secondary tumors were irradiated with either high-dose or low-dose of XRT with systemic anti-programmed cell death protein 1 and anti-cytotoxic T-lymphocyte associated protein 4 administration. Survival and tumor growth were monitored for the various groups, and secondary tumors were phenotyped by flow cytometry for immune populations. Tumor growth factor-beta (TGF-β) cytokine levels were assessed locally after low-dose XRT, and specific immune-cell depletion experiments were conducted to identify the major contributors to the observed systemic antitumor effect.ResultsThrough our preclinical and clinical studies, we observed that when tumor burden was high, there was a necessity of combining high-dose XRT to ‘prime’ T cells at the primary tumor site, with low-dose XRT directed to secondary (metastatic) tumors to ‘modulate the stroma’. Low-dose XRT improved the antitumor outcomes of checkpoint inhibitors by favoring M1 macrophage polarization, enhancing natural killer (NK) cell infiltration, and reducing TGF-β levels. Depletion of CD4+ T cells and NK cells abrogated the observed antitumor effect.ConclusionOur data extend the benefits of low-dose XRT to reprogram the tumor environment and improve the infiltration and function of effector immune cells into secondary tumors.


Author(s):  
A. Goyal ◽  
J. Carter ◽  
I.M. Pashtan ◽  
S. Gallotto ◽  
A. Niemierko ◽  
...  

Dose-Response ◽  
2021 ◽  
Vol 19 (4) ◽  
pp. 155932582110561
Author(s):  
Alexandra Jameus ◽  
Allison E. Kennedy ◽  
Christopher Thome

Cancer is the second leading cause of mortality worldwide accounting for almost 10 million deaths in 2020. Current standard of care treatment varies depending on the type and stage of disease, but commonly includes surgery, chemotherapy, and/or radiation therapy. There is evidence that whole- and half-body exposure to low dose ionizing radiation can also be an effective therapeutic due to its stimulation of anti-cancer immunity. One of the limiting factors for past clinical trials using low dose radiation therapy has been adverse hematological events. However, similar hematological changes are also frequently reported following standard of care treatments in oncology. This review summarizes the effects of various cancer therapies on hematologic toxicity through the evaluation of complete blood count reports. The reviewed literature elucidates hematological trends in patients undergoing chemotherapy, and both high and low dose radiation therapy. In general, high dose radiation and chemotherapy can result in widespread changes in blood counts, with the most severe effects related to leukopenia. Overall, compared to standard of care treatments, low dose radiation results in similar, yet more mild hematological changes. Taken together, hematological toxicities should not be a limiting factor in the applicability of low dose radiation as a cancer therapeutic.


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