Intratumoral expression of FoxP3-positive regulatory T-cells in T-cell lymphoma: no correlation with survival

Ups J Med Sci. 2019 Apr;124(2):105-110. doi: 10.1080/03009734.2018.1555195. Epub 2019 Mar 11.

Abstract

Background. In cancer, regulatory T-cells (Tregs) were previously believed to inhibit tumor immunity, leading to reduced survival. However, in hematologic malignancies, including T-cell lymphoma (TCL), a correlation between increased numbers of tumor-infiltrating Tregs and a favorable prognosis has been reported. We aimed to investigate the expression of the Treg biomarker forkhead box protein 3 (FoxP3) in TCL in immunocompetent individuals and explore a possible correlation to overall survival. Methods. In total, 35 diagnostic biopsies of TCL were stained using a FoxP3-specific monoclonal antibody (clone 236A/E7). Visual scoring was performed by counting positive cells in 15 high-power fields. Clinical data were collected retrospectively from medical records. Results. All the TCLs contained FoxP3+ cells, median 342 FoxP3+ cells/mm2 (range 1-3047). The degree of intratumoral expression of FoxP3 varied between the different subtypes of TCL, with the highest frequency found in angioimmunoblastic TCL. The frequency of intratumoral FoxP3+ cells had no impact on overall survival; neither when using a cutoff value of 200 FoxP3+ cells/mm2 (P = 0.84) nor with FoxP3 as a continuous variable (P = 0.63). Conclusions. Intratumoral Tregs are frequently found in TCL in immunocompetent individuals. In this heterogeneous group of TCL, there was no correlation between the density of intratumoral FoxP3+ cells and overall survival.

Keywords: FoxP3; T-cell lymphoma; Tregs; outcome; tumor microenvironment.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biopsy
  • Case-Control Studies
  • Denmark
  • Female
  • Forkhead Transcription Factors / metabolism*
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Immunosuppressive Agents
  • Lymphoma, T-Cell / metabolism*
  • Lymphoma, T-Cell / mortality*
  • Male
  • Middle Aged
  • Prognosis
  • Retrospective Studies
  • Sweden
  • T-Lymphocytes, Regulatory / cytology*
  • Treatment Outcome
  • Tumor Microenvironment
  • Young Adult

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Immunosuppressive Agents

Grants and funding

The work was supported by the Lion's Cancer Research Foundation.