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Correlation of low numbers of intratumoral FOXP3+ cells with worse progression-free survival in angioimmunoblastic T cell lymphoma
  1. Hung-Lin Liu1,
  2. Shao-Wen Weng2,3,
  3. Chih-Chi Chou4,
  4. Huey-Ling You5,6,
  5. Ming-Chung Wang1,
  6. Ming-Chun Ma1,
  7. Wan-Ting Huang3,4,5,6
  1. 1Department of Internal Medicine, Hematology-Oncology Division, Chang Gung Memorial Hospital Kaohsiung Branch, Kaohsiung, Taiwan
  2. 2Department of Internal Medicine, Chang Gung Memorial Hospital Kaohsiung Branch, Kaohsiung, Taiwan
  3. 3School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
  4. 4Department of Pathology, Chang Gung Memorial Hospital Kaohsiung Branch, Kaohsiung, Taiwan
  5. 5Department of Laboratory Medicine, Chang Gung Memorial Hospital Kaohsiung Branch, Kaohsiung, Taiwan
  6. 6Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan
  1. Correspondence to Dr Wan-Ting Huang, Chang Gung Memorial Hospital Kaohsiung Branch, Kaohsiung, Taiwan; huangwanting5{at}


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.

  • Epstein-Barr virus infections
  • lymphoma
  • immunohistochemistry

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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  • Handling editor Laurence de Leval.

  • Contributors HL-L: data acquisition and integrity, statistical analysis and overall manuscript writing. SW-W: statistical analysis and manuscript drafting. CC-C: histopathological review. HL-Y: histopathological review. MC-W: resources. MC-M: resources. WT-H: conceptualise and design the study, data interpretation, manuscript editing and guarantor.

  • Funding This study was supported by the Chang Gung Memorial Hospital (grant number CMRPG8L0461, OMRPG3E0031).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.