Permanent up-regulation of regulatory T-lymphocytes in patients with head and neck cancer

Abstract

Abstract. Various immune functions of different types of immune cells are strongly impaired in patients with head and neck squamous cell carcinoma (HNSCC). Regulatory T-lymphocyte cells (Tregs) have been suggested to be involved in the immunomodulation of immune responses and contribute to HNSCC progression and immune escape. 'Naturally' occurring CD4 + CD25 + Tregs represent a small fraction within the different subsets of regulatory T cells, which are known to inhibit numerous immune functions of different types of immune cells. In this study, the cellular ratio of CD4 + CD25high Tregs to the entire population of CD4 + T-lymphocytes was analyzed with respect to different stages of tumor progression and disease. Our data indicate a significantly high increased abundance of CD4 + CD25 high CD127 low Tregs in the peripheral blood of patients with HNSCC, which in addition show modulated expression levels of various functional proteins. Surprisingly, increased Treg levels were found even in patients with no active disease several years after tumor resection, with no significant correlation to the individual tumor stage. Additionally, increased levels of chemokine CCL22, which mediates migration of Tregs to the tumor, and upregulation of the corresponding receptor protein CCR4 were observed in HNSCC. Our data strongly suggest that HNSCC leads to a permanent shift of Treg levels with hardly recognizable recovery rates.

<p>A New Immunological Prognostic Model Based on Immunohistochemistry for Extranodal Natural Killer/T-Cell Lymphoma Patients After Non-Anthracycline-Based Chemotherapy</p>

“…[29][30][31] However, many studies showed that a low density of FoxP3+Tregs infiltrating the tumor microenvironment correlated with improved clinical outcomes in various human solid malignancies. 23,[26][27][28] This evidence suggests that the role of FoxP3+Tregs in the pathogenesis of solid tumors and hematological malignancies is different. FoxP3+Tregs may represent important lymphoma/host microenvironment modulators that participate in the regulation of the host immune response and biologic behavior of ENKTL.…”

“…The prognostic effect of FoxP3+Tregs remains debatable because it is associated with a poor prognosis in various solid malignancies. [26][27][28] whereas it has a better prognosis for hematologic malignancies. [29][30][31] However, little is known about the prognostic value of FoxP3+Tregs in patients with ENKTL.…”

A phase I dose escalation trial of MAGE-A3- and HPV16-specific peptide immunomodulatory vaccines in patients with recurrent/metastatic (RM) squamous cell carcinoma of the head and neck (SCCHN)

“…For example, regulatory T cells (Tregs), which suppress effector T cells and mediate peripheral tolerance are increased in the blood and tumor microenvironment in SCCHN patients. [39, 40] Myeloid derived suppressor cells (MDSC), which also have been found to be increased in the SCCHN tumor microenvironment, are known to suppress the immune response through secretion of IL-10, increasing Tregs and decreasing T cell activation and migration. [32, 41] Our understanding of the role that each of these elements plays, alone and collectively in the regulation of antitumor vaccine based immune responses, is hindered by the lack of post treatment tissue analysis, as findings in peripheral blood may not correlate with responses in the tumor microenvironment.…”