title: Low stromal Foxp3+ regulatory T-cell density is associated with complete response to neoadjuvant chemoradiotherapy in rectal cancer.
abstract: BACKGROUND
  Foxp3+ regulatory T cells (Tregs) play a vital role in preventing autoimmunity, but also suppress antitumour immune responses. Tumour infiltration by Tregs has strong prognostic significance in colorectal cancer, and accumulating evidence suggests that chemotherapy and radiotherapy efficacy has an immune-mediated component. Whether Tregs play an inhibitory role in chemoradiotherapy (CRT) response in rectal cancer remains unknown.
  
  
  METHODS
  Foxp3+, CD3+, CD4+, CD8+ and IL-17+ cell density in post-CRT surgical samples from 128 patients with rectal cancer was assessed by immunohistochemistry. The relationship between T-cell subset densities and clinical outcome (tumour regression and survival) was evaluated.
  
  
  RESULTS
  Stromal Foxp3+ cell density was strongly associated with tumour regression grade (P=0.0006). A low stromal Foxp3+ cell density was observed in 84% of patients who had a pathologic complete response (pCR) compared with 41% of patients who did not (OR: 7.56, P=0.0005; OR: 5.27, P=0.006 after adjustment for presurgery clinical factors). Low stromal Foxp3+ cell density was also associated with improved recurrence-free survival (HR: 0.46, P=0.03), although not independent of tumour regression grade.
  
  
  CONCLUSIONS
  Regulatory T cells in the tumour microenvironment may inhibit response to neoadjuvant CRT and may represent a therapeutic target in rectal cancer.
authors.affiliation: St John of God Subiaco Hospital, PO Box 14, Subiaco, WA 6904, Australia.|School of Medicine and Pharmacology, University of Western Australia, M503, 35 Stirling Highway, Crawley, WA 6009, Australia.
authors.forename: M J
authors.initials: MJ
authors.lastname: McCoy
authors.affiliation: St John of God Pathology, PO Box 646, Wembley, WA 6913, Australia.|School of Surgery, University of Western Australia, M507, 35 Stirling Highway, Crawley, WA 6009, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Hemmings
authors.affiliation: St John of God Subiaco Hospital, PO Box 14, Subiaco, WA 6904, Australia.|School of Surgery, University of Western Australia, M507, 35 Stirling Highway, Crawley, WA 6009, Australia.
authors.forename: T J
authors.initials: TJ
authors.lastname: Miller
authors.affiliation: St John of God Subiaco Hospital, PO Box 14, Subiaco, WA 6904, Australia.
authors.forename: S J
authors.initials: SJ
authors.lastname: Austin
authors.affiliation: Institute for Health Research, University of Notre Dame, PO Box 1225, Fremantle, WA 6959, Australia.
authors.forename: M K
authors.initials: MK
authors.lastname: Bulsara
authors.affiliation: St John of God Subiaco Hospital, PO Box 14, Subiaco, WA 6904, Australia.|School of Surgery, University of Western Australia, M507, 35 Stirling Highway, Crawley, WA 6009, Australia.
authors.forename: N
authors.initials: N
authors.lastname: Zeps
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, M503, 35 Stirling Highway, Crawley, WA 6009, Australia.|Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, WA 6009, Australia.
authors.forename: A K
authors.initials: AK
authors.lastname: Nowak
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, M503, 35 Stirling Highway, Crawley, WA 6009, Australia.
authors.forename: R A
authors.initials: RA
authors.lastname: Lake
authors.affiliation: St John of God Subiaco Hospital, PO Box 14, Subiaco, WA 6904, Australia.|School of Surgery, University of Western Australia, M507, 35 Stirling Highway, Crawley, WA 6009, Australia.
authors.forename: C F
authors.initials: CF
authors.lastname: Platell
mesh_terms: D000368:Aged; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors