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Aberrant frequency of TNFR2-expressing CD4+ FoxP3+ regulatory T cells in nasopharyngeal carcinoma patients

Engku Nur Syafirah Engku Abd Rahman1, Ahmad Adebayo Irekeola2, Rafidah Hanim Shueb1

  • 1Department of Medical Microbiology and Parasitology, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150 Kubang Kerian, Kelantan, Malaysia.

Cytokine
|September 1, 2023
PubMed

Insights

Tumor necrosis factor receptor 2 (TNFR2) is elevated on regulatory T cells (Tregs) in nasopharyngeal carcinoma (NPC) patients. TNFR2+ Tregs correlate with advanced disease and poor prognosis, suggesting TNFR2 as a predictive biomarker for NPC.

Area of Science:

  • Immunology
  • Oncology

Background:

  • Regulatory T cells (Tregs) expressing CD4 and FoxP3 are crucial for immune suppression.
  • Tumor necrosis factor receptor 2 (TNFR2) is a surface marker on highly suppressive CD4+ FoxP3+ Tregs.
  • Nasopharyngeal carcinoma (NPC) is a malignancy where immune cell dynamics play a significant role.

Purpose of the Study:

  • To investigate TNFR2 expression on Tregs in NPC patients compared to healthy controls.
  • To assess the functional capacity (proliferation, migration, survival) of TNFR2+ Tregs.
  • To determine the association between TNFR2+ Tregs and clinicopathological characteristics, including prognosis.

Main Methods:

  • Flow cytometry was used to quantify TNFR2 expression on Tregs in peripheral blood (PB) and tumor microenvironment (TME) of NPC patients and healthy controls.
  • Functional assays assessed Treg proliferation, migration, and survival.
  • Cytokine expression levels (IL-6, IL-10, IFN-γ, TNF-α) were measured.
  • Correlation analysis was performed between TNFR2 expression and clinicopathological features.

Main Results:

  • NPC patients exhibited significantly higher TNFR2 expression on Tregs in both PB and TME compared to conventional T cells.
  • TNFR2 expression correlated better with FoxP3 than CD25 or CD127 in NPC PB.
  • While no direct association with Treg function was found, TNFR2+ Tregs from NPC patients demonstrated enhanced proliferation, migration, and survival, along with higher levels of IL-6, IL-10, IFN-γ, and TNF-α compared to controls.
  • TNFR2 expression on suppressive Tregs was linked to WHO Type III histology, distant metastasis, progressive disease, and poor prognosis.

Conclusions:

  • TNFR2 is significantly upregulated on Tregs in NPC patients.
  • TNFR2+ Tregs in NPC exhibit heightened functional capacity and express higher levels of key cytokines.
  • TNFR2 expression on Tregs serves as a potential predictive biomarker for disease progression and poor prognosis in NPC.
Keywords:
Nasopharyngeal carcinomaTNFR2Tumour microenvironmentregulatory T cells

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