title: Radiation enhances regulatory T cell representation.
abstract: OBJECTIVE
  Immunotherapy could be a useful adjunct to standard cytotoxic therapies such as radiation in patients with micrometastatic disease, although successful integration of immunotherapy into treatment protocols will require further understanding of how standard therapies affect the generation of antitumor immune responses. This study was undertaken to evaluate the impact of radiation therapy (RT) on immunosuppressive T regulatory (Treg) cells.
  
  
  METHODS
  Treg cells were identified as a CD4(+)CD25(hi)Foxp3(+) lymphocyte subset, and their fate was followed in a murine TRAMP C1 model of prostate cancer in mice with and without RT.
  
  
  RESULTS
  CD4(+)CD25(hi)Foxp3(+) Treg cells increased in immune organs after local leg or whole-body radiation. A large part, but not all, of this increase after leg-only irradiation could be ascribed to radiation scatter and Treg cells being intrinsically more radiation resistant than other lymphocyte subpopulations, resulting in their selection. Their functional activity on a per-cell basis was not affected by radiation exposure. Similar findings were made with mice receiving local RT to murine prostate tumors growing in the leg. The importance of the Treg cell population in the response to RT was shown by systemic elimination of Treg cells, which greatly enhanced radiation-induced tumor regression.
  
  
  CONCLUSIONS
  We conclude that Treg cells are more resistant to radiation than other lymphocytes, resulting in their preferential increase. Treg cells may form an important homeostatic mechanism for tissues injured by radiation, and in a tumor context, they may assist in immune evasion during therapy. Targeting this population may allow enhancement of radiotherapeutic benefit through immune modulation.
authors.affiliation: Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1714, USA.
authors.forename: Evelyn L
authors.initials: EL
authors.lastname: Kachikwu
authors.forename: Keisuke S
authors.initials: KS
authors.lastname: Iwamoto
authors.forename: Yu-Pei
authors.initials: YP
authors.lastname: Liao
authors.forename: John J
authors.initials: JJ
authors.lastname: DeMarco
authors.forename: Nzhde
authors.initials: N
authors.lastname: Agazaryan
authors.forename: James S
authors.initials: JS
authors.lastname: Economou
authors.forename: William H
authors.initials: WH
authors.lastname: McBride
authors.forename: Dörthe
authors.initials: D
authors.lastname: Schaue
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000532:radiotherapy; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D051927:CD24 Antigen / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000528:radiation effects; D045744:Cell Line, Tumor; D004307:Dose-Response Relationship, Radiation; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis*; D006614:Hindlimb / Q000528:radiation effects; D007167:Immunotherapy; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis*; D008198:Lymph Nodes / Q000166:cytology; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011471:Prostatic Neoplasms / Q000276:immunology / Q000532:radiotherapy; D011836:Radiation Tolerance / Q000276:immunology; D012542:Scattering, Radiation; D013154:Spleen / Q000166:cytology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000528:radiation effects*; D014916:Whole-Body Irradiation
chemical_list: D015415:Biomarkers; D051927:CD24 Antigen; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C508018:Il2ra protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit