Relationships between regulatory T cells and CD8+ effector populations in patients with squamous cell carcinoma of the head and neck

Authors

  • Kazuaki Chikamatsu MD,

    Corresponding author
    1. Department of Otolaryngology—Head and Neck Surgery, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan
    • Department of Otolaryngology—Head and Neck Surgery, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan
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  • Koichi Sakakura MD,

    1. Department of Otolaryngology—Head and Neck Surgery, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan
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  • Theresa L. Whiteside PhD,

    1. Department of Pathology, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213-1863
    2. Department of Immunology, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213-1863
    3. Department of Otolaryngology, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213-1863
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  • Nobuhiko Furuya MD

    1. Department of Otolaryngology—Head and Neck Surgery, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan
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Abstract

Background

Homeostasis of circulating T cells is regulated in complex ways that have not yet been well defined. The balance between type 1 and type 2 T-cell subsets in cancer patients is thought to modulate antitumor immunity. Meanwhile, CD4+CD25+ regulatory T cells (Treg), which are potent inhibitors of antitumor immune responses, also play an invaluable role in maintaining immune homeostasis.

Methods

Peripheral blood was obtained from 42 patients with squamous cell carcinoma of the head and neck (SCCHN) and 24 healthy age-selected donors. The percentages of T-cell subsets and their cytokine profiles expressed in response to ex vivo stimulation were studied by multicolor flow cytometry.

Results

Although patients with SCCHN had a lower percentage (p < .05) of circulating CD4+ T cells than healthy donors, CD4+CD25+ regulatory T cells (Treg) were increased in the patients (p < .01). A significant increase in Th1 and Th2 CD4+ T cells was observed in the patients after ex vivo stimulation with phorbol 12-myristate 13-acetate /ionomycin. The percent of Treg inversely correlated with that of total CD8+ T cells (p < .05), CD8+IFN-γ+ (Tc1) cells (p < .05), and CD8+IL-4+ (Tc2) cells (p < .01). There was a highly significant correlation between Tc1 and Tc2 CD8+ T cells (p < .0001) in SCCHN patients but not in controls.

Conclusions

Treg are increased in proportion in the circulation of patients with SCCHN. These cells appear to downregulate cytokine expression in both Tc1 and Tc2 subsets of CD8+ effector T cells, which may be responsible for antitumor responses. © 2006 Wiley Periodicals, Inc. Head Neck 2007

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