title: Radiotherapy suppressed tumor-specific recruitment of regulator T cells via up-regulating microR-545 in Lewis lung carcinoma cells.
abstract: OBJECTIVE
  Radiotherapy is an important treatment for cancer. The main irradiated action is thought to be the irreversible damage to tumor cell DNA, but recent studies showed that high dose radiotherapy related to the tumor immune response. This study was designed to determine the relationship between Lewis lung tumor radiosensitivity and CD4+CD25+ regulatory T cells (Tregs) infiltration and elucidate the underlying mechanisms in vitro.
  
  
  METHODS
  With tumor transplantation method to establish mice Lewis lung tumor mice model, to observe the inhibition rate of radiotherapy to tumor growth. Proliferation profiles of CD4+CD25+ Tregs and CD4+ T cells were assessed by flow cytometry. MiR-545 and CCL-22 mRNA were determined by Quantitative Real-Time PCR. CCL-22 protein was determined by western blot assay.
  
  
  RESULTS
  Radiotherapy caused a time-dependent inhibition of tumor growth as well as a decrease in the percentage of tumor-infiltrating CD4+CD25+ Tregs of CD4+ T cells compared with no treatment group. And the miR-545 was significantly upregulated and CCL-22 was significantly down-regulated in irradiated tumor and Lewis lung cancer cells. In Lewis lung cancer cell transfection experiments, mimic or inhibitor for miR-545 negatively regulated CCL-22 expression when cells treated or treated without irradiation. Silenced miR-545 promotes CD4+CD25+ Treg proliferation. Additionally, silenced miR-545 reversed radiosensitivity of Lewis lung cancer.
  
  
  CONCLUSIONS
  Radiotherapy suppressed specific recruitment of regulator CD4+CD25+ Treg cells in Lewis lung carcinoma via up-regulating microR-545.
authors.affiliation: Department of Radiotherapy, Nanjing Chest Hospital Affiliated to Southeast University Nanjing 210029, Jiangsu, P. R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Liao
authors.affiliation: Department of Radiotherapy, Nanjing Chest Hospital Affiliated to Southeast University Nanjing 210029, Jiangsu, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Department of Radiotherapy, Nanjing Chest Hospital Affiliated to Southeast University Nanjing 210029, Jiangsu, P. R. China.
authors.forename: Nuo
authors.initials: N
authors.lastname: Zhu
authors.affiliation: Department of Radiotherapy, Nanjing Chest Hospital Affiliated to Southeast University Nanjing 210029, Jiangsu, P. R. China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Radiotherapy, Nanjing Chest Hospital Affiliated to Southeast University Nanjing 210029, Jiangsu, P. R. China.
authors.forename: Jiu
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Radiotherapy, Nanjing Chest Hospital Affiliated to Southeast University Nanjing 210029, Jiangsu, P. R. China.
authors.forename: Yanhu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Radiotherapy, Nanjing Chest Hospital Affiliated to Southeast University Nanjing 210029, Jiangsu, P. R. China.
authors.forename: Mei
authors.initials: M
authors.lastname: Hong
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018827:Carcinoma, Lewis Lung / Q000235:genetics* / Q000276:immunology* / Q000532:radiotherapy*; D054422:Chemokine CCL22 / Q000096:biosynthesis; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D016246:Lymphocytes, Tumor-Infiltrating / Q000528:radiation effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000096:biosynthesis / Q000528:radiation effects*; D011836:Radiation Tolerance / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000528:radiation effects*; D014162:Transfection; D015854:Up-Regulation
chemical_list: C515483:Ccl22 protein, mouse; D054422:Chemokine CCL22; D035683:MicroRNAs
keywords: CCL-22; CD4+CD25+ T regulator cells; Lewis lung cancer cells; miR-545; radiotherapy; tumor xenograft