title: Effects of radiation on T regulatory cells in normal states and cancer: mechanisms and clinical implications.
abstract: Radiation remains an important component of cancer treatment. In addition to inducing tumor cell death through direct cytotoxic effects, radiation can also promote the regression of tumor via augment of immune response. Regulatory T cells (Tregs) are a unique subpopulation of CD4 positive cells, which are characterized by expression of the forkhead box P3 (Foxp3) transcription factor and high levels of CD25. Mounting evidence has shown that Tregs are implicated in the development and progression of various types of cancer, which makes Tregs an important target in cancer therapeutics. Generally, lymphocytes are regarded as radiosensitive. However, Tregs have been demonstrated to be relatively resistant to radiotherapy, which is partly mediated by downregulation of pro-apoptotic proteins and upregulation of anti-apoptotic proteins. Moreover, radiotherapy can increase the production of Tregs and the recruitment of Tregs to local tumor microenvironment. Tregs can attenuate radiation-induced tumor death, which cause the resistance of tumor to radiotherapy. Recent experimental studies and clinical trails have demonstrated that the combination of radiation with medications that target Tregs is promising in the treatment of several types of neoplasms. In this review, we discussed the effect of radiation on Tregs in physiological states and cancer. Further, we presented an overview of therapies that target Tregs to enhance the efficacy of radiation in cancer therapeutics.
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University Nanjing 210029, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Radiotherapy, The 81st Hospital of PLA Nanjing 210002, China.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University Nanjing 210029, China.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University Nanjing 210029, China.
authors.forename: Hongcheng
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University Nanjing 210029, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Oncology, Taizhou People's Hospital Taizhou 225300, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Department of Radiation Oncology, Huai'an First People's Hospital, Nanjing Medical University Nanjing 223300, Jiangsu, China.
authors.forename: Yaqi
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University Nanjing 210029, China.
authors.forename: Xinchen
authors.initials: X
authors.lastname: Sun
keywords: Regulatory T cell; T regulatory cells; Tregs; cancer; immune response; radiation; radiotherapy