Stains
FOXP3

Author: Emeka Enwere, M.D., Satbir Thakur, Ph.D. (see Authors page)

Revised: 20 September 2016, last major update September 2016

Copyright: (c) 2002-2016, PathologyOutlines.com, Inc.

PubMed Search: FOXP3 [title] stain

Cite this page: FOXP3. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/stainsfoxp3.html. Accessed October 18th, 2017.
Definition / general
  • FOXP3 (Forkhead box P3) is a member of the FOX protein (forkhead / winged helix) family and acts as a master regulator of the development and function of regulatory T cells (Science 2003;299:1057)
  • It is a specific marker of both natural T regulatory cells (nTregs) and adaptive / induced T regulatory cells (a / iTregs) (Immunity 2005;22:329)
  • This can play an important role in immune destruction of cancer cells and various autoimmune diseases
Essential features
  • Acts as a transcriptional regulator of regulatory T cells (Tregs)
  • Plays an essential role in maintaining homeostasis of the immune system by regulating the suppressive function, stability and expansion of the Tregs
  • Depending upon its interaction with various histone deacetylases or acetylases, FOXP3 can act both as a transcriptional activator or repressor in Tregs (GeneCards - FOXP3)
  • Orchestrates the expression levels of proteins like CTLA4, IL2, IL17, IFN-ϒ, RORA, RORC and RELA, resulting in inhibition of effector and helper T cells as well as expansion of Tregs (Proc Natl Acad Sci USA 2005;102:5138, Nature 2007;446:685, Nature 2008;453:236, J Immunol 2008;180:4785)
Terminology
Also known as:
  • Scurfin, IPEX, DIETER, AIID, PIDX, XPID, JM2, FOXP3delta7
  • Mutations cause IPEX syndrome - Immune dysregulation, polyendocrinopathy, enteropathy, x-linked immunodeficiency (GeneCards - FOXP3)
Sites
Pathophysiology
  • Induction of FOXP3 positive Treg cells has been reported to markedly reduce autoimmune disease severity in animal models of diabetes, multiple sclerosis, asthma, inflammatory bowel disease, thyroiditis and renal disease (Springer Semin Immunopathol 2006;28:3)
  • In mice, a 'Scurfy' phenotype is observed due to a mutant FOXP3 (lacking Forkhead domain); these mice demonstrate hyperproliferation of CD4+ T lymphocytes, extensive multiorgan infiltration and elevation of numerous cytokines (Nat Genet 2001;27:68)
  • In humans, patients with solid tumors show increased local FOXP3 positive T cells, which can inhibit the suppression of cancerous cells by the immune system (Blood 2006;108:804); conversely, FOXP3 positive Tregs are dysfunctional in autoimmune disease such as systemic lupus erythematosus (SLE) (J Autoimmun 2006;27:110)
Clinical features
Prognostic factors
  • Increased FOXP3 expression in muscle invading urinary bladder cancer is associated with reduced long term survival (BJU Int 2011;108:1672)
  • In breast cancer, increasing FOXP3 expression is associated with reduced overall survival; FOXP3 is also a strong prognostic factor for distant metastases free survival (J Clin Oncol 2009;27:1746)
  • In colorectal carcinoma, high FOXP3 expression in cancer cells are associated with poor prognosis: in these patients, FOXP3 levels in tumor infiltrating Treg cells did not correlate with overall patient survival (PLoS One 2013;8:e53630)
  • In smokers with adenocarcinoma of the lung, high FOXP3 / CD4 T cells correlated with poor survival (Ann Oncol 2016 Aug 8 [Epub ahead of print])
Microscopic (histologic) images

Images hosted on other servers:

FOXP3 expression in prostate cancer

FOXP3 expression in glioblastoma

FOXP3 expression in normal lymph node

Positive stains
Negative stains
Additional references