title: FOXP3 subcellular localization predicts recurrence in oral squamous cell carcinoma.
abstract: Forkhead box protein P3 (FOXP3) expression in tumor infiltrating CD4(+)T cells is generally associated with an intrinsic capacity to suppress tumor immunity. Based on this notion, different studies have evaluated the prognostic value of this maker in cancer but contradictory results have been found. Indeed, even within the same cancer population, the presence of CD4(+)FOXP3(+)T cells has been associated,with either a poor or a good prognosis, or no correlation has beenfound. Here, we demonstrate,in patients with oral squamous cell carcinoma (OSCC), that what really represents a prognostic parameter is not the overall expression of FOXP3 but its intracellular localization.While overallFOXP3 expression in tumor infiltrating CD4(+)T cells does not correlate with tumor recurrence, its intracellular localization within the CD4 cells does: nuclear FOXP3 (nFOXP3) is associated with tumor recurrence within 3 years, while cytoplasmicFOXP3 (cFOXP3) is associated with a lower likelihood of recurrence. Thus, we propose elevated levels of the cFOXP3/nFOXP3 ratio within tumor infiltrating CD4(+) T cells as a predictor of OSCC recurrence.
authors: Department of Otolaryngology, University of Miami, Miller School of Medicine, Miami, Florida, United States of America ; Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida, United States of America.
authors: Donald T
authors: DT
authors: Weed
authors: Gail
authors: G
authors: Walker
authors: Adriana C
authors: AC
authors: De La Fuente
authors: Ronen
authors: R
authors: Nazarian
authors: Jennifer L
authors: JL
authors: Vella
authors: Carmen R
authors: CR
authors: Gomez-Fernandez
authors: Paolo
authors: P
authors: Serafini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D002467:Cell Nucleus / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000276:immunology / Q000378:metabolism*; D011379:Prognosis; D021381:Protein Transport; D012372:ROC Curve; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors
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