title: Inhibition of IL-17A suppresses enhanced-tumor growth in low dose pre-irradiated tumor beds.
abstract: 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.
authors.affiliation: Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, Yonsei University, Seoul, Korea.
authors.forename: Hyo Jin
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Ik-Jae
authors.initials: IJ
authors.lastname: Lee
authors.affiliation: Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Won Woo
authors.initials: WW
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, Yonsei University, Seoul, Korea.
authors.forename: Sang-Jun
authors.initials: SJ
authors.lastname: Ha
authors.affiliation: Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Yang-Gun
authors.initials: YG
authors.lastname: Suh
authors.affiliation: Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jinsil
authors.initials: J
authors.lastname: Seong
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D018450:Disease Progression; D004307:Dose-Response Relationship, Radiation; D020381:Interleukin-17 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008198:Lymph Nodes / Q000473:pathology / Q000528:radiation effects; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D008297:Male; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000276:immunology / Q000473:pathology* / Q000532:radiotherapy*; D009500:Neutralization Tests; D011839:Radiation, Ionizing; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D057134:Antibodies, Neutralizing; D020381:Interleukin-17; D015850:Interleukin-6; D016212:Transforming Growth Factor beta