Correlation of low numbers of intratumoral FOXP3+ cells with worse progression-free survival in angioimmunoblastic T cell lymphoma

J Clin Pathol. 2024 Oct 20;77(11):743-750. doi: 10.1136/jcp-2023-208932.

Abstract

Aims: Angioimmunoblastic T cell lymphoma (AITL) is a T cell lymphoma with aberrant immune activity. It is characterised by inflammatory and immune reactions. However, the impact of regulatory T (Treg) cells on AITL remains unclear.

Methods: We retrospectively collected 46 AITL cases and performed immunohistochemical analysis of forkhead box P3 (FOXP3) expression. The number of immunostained FOXP3 cells was determined using a digital pathology system with whole-slide imaging. The average number of FOXP3+ cells per high-power field (HPF) was determined by randomly counting 20 HPFs. AITL cases were categorised into high-expression and low-expression groups based on the median count of FOXP3+ cells in all analysed samples. The relationship between FOXP3 expression and clinicopathological features was assessed.

Results: Among the studied patients, 14 (30.4%) were females and 32 (69.6%) were males, and the median age at diagnosis was 64.1 years. The median expression of FOXP3 was 84.9 positive cells/HPF. FOXP3 expression negatively correlated with Epstein-Barr virus-encoded small RNA positivity in tumour (p=0.041). The patients with low FOXP3 expression presented with aggressive clinical behaviour, including advance-staged diseases (p=0.043), splenomegaly (p=0.008), B symptoms (p=0.019) and extranodal involvement (p=0.019). The neutrophil-to-lymphocyte ratio was higher in the patients with low FOXP3 expression, compared with those with high FOXP3 expression. Low FOXP3 expression had an adverse effect on progression-free survival (PFS, p=0.033), and increased the risk of recurrence 2.320-fold (HR 2.320 (95% CI 1.109 to 4.856); p=0.025).

Conclusions: Patients with AITL with low FOXP3 expression tend to have aggressive clinical presentation and shortened PFS. These findings may help with risk stratification and determination of new treatment strategy.

Keywords: Epstein-Barr virus infections; immunohistochemistry; lymphoma.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / metabolism
  • Female
  • Forkhead Transcription Factors* / analysis
  • Forkhead Transcription Factors* / metabolism
  • Humans
  • Immunoblastic Lymphadenopathy / immunology
  • Immunoblastic Lymphadenopathy / metabolism
  • Immunoblastic Lymphadenopathy / pathology
  • Immunohistochemistry
  • Lymphoma, T-Cell / immunology
  • Lymphoma, T-Cell / metabolism
  • Lymphoma, T-Cell / mortality
  • Lymphoma, T-Cell / pathology
  • Male
  • Middle Aged
  • Progression-Free Survival*
  • Retrospective Studies
  • T-Lymphocytes, Regulatory* / immunology

Substances

  • Forkhead Transcription Factors
  • FOXP3 protein, human
  • Biomarkers, Tumor