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The Frequency and Suppressor Function of CD4⁺CD25^highFoxp3⁺ T Cells in the Circulation of Patients with Squamous Cell Carcinoma of the Head and Neck

Authors' Affiliation: Suite 1.27, Research Pavilion at the Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania

Requests for reprints: Theresa L. Whiteside, Research Pavilion at the Hillman Cancer Center, University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Suite 1.27, Pittsburgh, PA 15213-1863. Phone: 412-624-0096; Fax: 412-624-0264; E-mail: whitesidetl{at}upmc.edu.

Objective: Immune escape is a characteristic feature of head and neck squamous cell carcinoma (HNSCC). Regulatory T cells (Treg) might contribute to HNSCC progression by suppressing antitumor immunity, and their attributes in patients are of special interest.

Methods: Multicolor flow cytometry was used to study the frequency and phenotype of Treg in peripheral blood lymphocytes of 35 patients with HNSCC and 15 normal controls (NC). CD4⁺CD25^high T cells were purified by fluorescence-activated cell sorting and tested for regulatory function by coculture with carboxyfluorescein diacetate succinimidylester–labeled autologous CD4⁺CD25^– responder cells.

Results: The percentages of circulating CD4⁺CD25⁺ T cells were increased in HNSCC patients (5 ± 3%) versus NC (2 ± 1.5%). In patients, this cell subset largely contained CD4⁺CD25^highFoxp3⁺ T cells and only few CD25^low/interm cells. In addition, the frequency of Treg positive for CD62L, CTLA-4, Fas, FasL, and Foxp3 was greater in the circulation of patients than in NC (P < 0.0001). In HNSCC patients, Treg mediated significantly higher suppression (78 ± 7%) compared with Treg in NC (12 ± 4%) with P < 0.0001. Surprisingly, higher Treg frequency (P < 0.0059) and levels of suppression (P < 0.0001) were observed in patients with no evident disease (NED) than in untreated patients with active disease (AD).

Conclusions: The frequency of T cells with suppressor phenotype and function (Treg) was significantly greater in HNSCC patients who were NED after oncologic therapy relative to those with AD. This finding suggests that oncologic therapy favors expansion of Treg.

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				C. Bergmann, L. Strauss, Y. Wang, M. J. Szczepanski, S. Lang, J. T. Johnson, and T. L. Whiteside T Regulatory Type 1 Cells in Squamous Cell Carcinoma of the Head and Neck: Mechanisms of Suppression and Expansion in Advanced Disease Clin. Cancer Res., June 15, 2008; 14(12): 3706 - 3715. [Abstract] [Full Text] [PDF]