title: FOXP3+ T regulatory lymphocytes in primary melanoma are associated with BRAF mutation but not with response to BRAF inhibitor.
abstract: Tumour infiltrating lymphocytes in primary melanoma have been found to correlate with patient outcomes. A subpopulation of tumour infiltrating lymphocytes expresses the transcription factor forkhead box protein 3 (FOXP3). These are known as FOXP3+ T-regulatory cells (Tregs) and are thought to play an immune suppressive role in tumourigenesis. In most tumours, including melanoma, a high density of intratumoural FOXP3+ Tregs has been associated with poor prognosis. It is not known whether these cells also influence the response to BRAF inhibition therapy in metastatic melanoma. In the present study we retrospectively investigated the density of FOXP3+ Tregs in primary melanomas, with known subsequent metastasis, in relation to various clinicopathological parameters including BRAF and NRAS mutation status, and response to BRAF inhibitor therapy. The intratumoural density of FOXP3+ Tregs was two-fold higher in melanomas with mutant BRAF compared to those with wild type BRAF status (p = 0.03). In patients treated with BRAF kinase inhibitors FOXP3+ Treg density in the primary tumour was not predictive of treatment response (p = 0.38).
authors: 1Department of Anatomical Pathology, Pathwest Laboratory Medicine, Queen Elizabeth II Medical Centre 2Department of Medical Oncology, Sir Charles Gairdner Hospital 3Centre for Applied Statistics, University of Western Australia 4Department of Research, Sir Charles Gairdner Hospital 5School of Surgery, University of Western Australia 6School of Pathology and Laboratory Medicine, University of Western Australia 7School of Medicine and Pharmacology, University of Western Australia, WA, Australia.
authors: Connull
authors: C
authors: Leslie
authors: Samantha E
authors: SE
authors: Bowyer
authors: Alison
authors: A
authors: White
authors: Fabienne
authors: F
authors: Grieu-Iacopetta
authors: Michelle
authors: M
authors: Trevenen
authors: Barry
authors: B
authors: Iacopetta
authors: Benhur
authors: B
authors: Amanuel
authors: Michael
authors: M
authors: Millward
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D004252:DNA Mutational Analysis; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology*; D008875:Middle Aged; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics* / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D047428:Protein Kinase Inhibitors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf