FOXP3 is a forkhead transcription factor family member involved in T-cell regulation, activation and differentiation. FOXP3 has been shown to be a master control gene for the development and function of CD4+/CD25+ regulatory T-cells. In IHC, FOXP3 has been shown to be a specific marker for adult T-cell leukemia/lymphoma (1). In melanoma and in breast and lung cancers, high numbers of circulating regulatory T-cells have been associated with disease progression (2-5). Conversely, the infiltration of FOXP3+ regulatory T cells into invasive tumors has also been reported to be associated with survival in a variety of cancers (2-7). In colon cancers, a high frequency of FOXP3+ infiltrates has shown to be a positive indicator (6-7). Patients with high FOXP3 expression in Crohn’s disease have shown a better response to infliximab therapy (8). In allography recipients, FOXP3 cell levels may also be useful in improving post-transplant management (9).
1. Roncador G, et al. FOXP3, a selective marker for a subset of adult T-cell leukaemia/lymphoma. Leukemia. 2005 Dec; 19(12):2247-53.
2. Gerber AL, et al. High expression of FOXP3 in primary melanoma is associated with tumor progression. Br J Dermatol. 2014 Jan; 170(1):103-9.
3. Ali HR, et al. Association between CD8+ T-cell infiltration and breast cancer survival in 12,439 patients. Ann Oncol. 2014 Aug; 25(8):1536-43.
4. Liu H, et al. Tumor-infiltrating lymphocytes predict response to chemotherapy in patients with advance non-small cell lung cancer. Cancer Immunol Immunother. 2012 Oct; 61(10):1849-56.
5. Tao H, et al. Density of tumor-infiltrating FOXP3+ T cells as a response marker for induction chemoradiotherapy and a potential prognostic factor in patients treated with trimodality therapy for locally advanced non-small cell lung cancer. Ann Thorac Cardiovasc Surg. 2014; 20(6):980-6.
6. Ling A, et al. The intratumoural subsite and relation of CD8(+) and FOXP3(+) T lymphocytes in colorectal cancer provide important prognostic clues. Br J Cancer. 2014 May 13; 110(10):2551-9.
7. Frey DM, et al. High frequency of tumor-infiltrating FOXP3(+) regulatory T cells predicts improved survival in mismatch repair-proficient colorectal cancer patients. Int J Cancer. 2010 Jun 1; 126(11):2635-43.
8. Sloan S, et al. FOXP3+ regulatory T-cell counts correlate with histological response in Crohn’s colitis treated with infliximab. Pathol Int. 2014 Dec; 64(12):624-7.
9. Stenard F, et al. Decreases in circulating CD4+CD25hiFOXP3+ cells and increases in intragraft FOXP3+ cells accompany allograft rejection in pediatric liver allograft recipients. Pediatr Transplant. 2009 Feb; 13(1):70-80.
10. Center for Disease Control Manual. Guide: Safety Management, NO. CDC-22, Atlanta, GA. April 30, 1976 “Decontamination of Laboratory Sink Drains to Remove Azide Salts.”
11. Clinical and Laboratory Standards Institute (CLSI). Protection of Laboratory Workers from Occupationally Acquired Infections; Approved Guideline-Fourth Edition CLSI document M29-A4 Wayne, PA 2014.