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Inhibition of IL-17A Suppresses Enhanced-Tumor Growth in Low Dose Pre-Irradiated Tumor Beds

 Eun-Jung Lee  ;  Hyo Jin Park  ;  Ik-Jae Lee  ;  Won Woo Kim  ;  Sang-Jun Ha  ;  Yang-Gun Suh  ;  Jinsil Seong 
 PLOS ONE, Vol.9(9) : e106423, 2014 
Journal Title
Issue Date
Animals ; Antibodies, Neutralizing/pharmacology ; Cell Differentiation/drug effects ; Cell Differentiation/radiation effects ; Cell Proliferation/drug effects ; Cell Proliferation/radiation effects ; Disease Progression ; Dose-Response Relationship, Radiation ; Interleukin-17/antagonists & inhibitors* ; Interleukin-17/metabolism ; Interleukin-6/metabolism ; Lymph Nodes/pathology ; Lymph Nodes/radiation effects ; Lymphocytes, Tumor-Infiltrating/drug effects ; Lymphocytes, Tumor-Infiltrating/immunology ; Lymphocytes, Tumor-Infiltrating/radiation effects ; Male ; Mice, Inbred C3H ; Neoplasm Transplantation ; Neoplasms/immunology ; Neoplasms/pathology* ; Neoplasms/radiotherapy* ; Neutralization Tests ; Radiation, Ionizing ; Th17 Cells/drug effects ; Th17 Cells/immunology ; Th17 Cells/radiation effects ; Transforming Growth Factor beta/metabolism
Ionizing radiation induces modification of the tumor microenvironment such as tumor surrounding region, which is relevant to treatment outcome after radiotherapy. In this study, the effects of pre-irradiated tumor beds on the growth of subsequently implanted tumors were investigated as well as underlying mechanism. The experimental model was set up by irradiating the right thighs of C3H/HeN mice with 5 Gy, followed by the implantation of HCa-I and MIH-2. Both implanted tumors in the pre-irradiated bed showed accelerated-growth compared to the control. Tumor-infiltrated lymphocyte (TIL) levels were increased, as well as pro-tumor factors such as IL-6 and transforming growth factor-beta1 (TGF-β1) in the pre-irradiated group. In particular, the role of pro-tumor cytokine interleukin-17A (IL-17A) was investigated as a possible target mechanism because IL-6 and TGF-β are key factors in Th17 cells differentiation from naïve T cells. IL-17A expression was increased not only in tumors, but also in CD4+ T cells isolated from the tumor draining lymph nodes. The effect of IL-17A on tumor growth was confirmed by treating tumors with IL-17A antibody, which abolished the acceleration of tumor growth. These results indicate that the upregulation of IL-17A seems to be a key factor for enhancing tumor growth in pre-irradiated tumor beds.
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1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
Yonsei Authors
Suh, Yang Gun(서양권)
Seong, Jin Sil(성진실) ORCID logo https://orcid.org/0000-0003-1794-5951
Lee, Eun Jung(이은정)
Lee, Ik Jae(이익재) ORCID logo https://orcid.org/0000-0001-7165-3373
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