T Regulatory Cells and Cancer

In humans, most authors agree that numbers of naturally occurring T cells with regulatory function (Tregs) increase with age and that the frequency of inducible regulatory T cells declines [reviewed in 78]. The increase of Tregs in ageing patients could impose a regulatory/suppressive environment and thus contribute to tumor development.

El Andaloussi et al. [79] evaluated 10 patients (female mean age 60 years, male mean age 52 years) with glioblastoma and found in total CD3+ T cells a significant increase in tumor and peripheral blood of Foxp3+ T regulatory cells (55.1 % ± 1.88 % and 33.4 % ± 1.95 % respectively) in comparison with healthy donors (15.6 % ± 0.76 %). Sorted CD4+CD25+ (Treg) cells suppressed the proliferation of stimulated CD4+CD25- T cells suggesting that the expansion of suppressive Treg cells in glioma patients may downregulate the antitumor response in the central nervous system. In agreement, Hiraoka et al. [80] found in patients with pancreas ductal adenocarcinoma (n = 198 mean age 62 ± 10 years) a prevalence of Treg cells in tissue-infiltrating (stroma) lymphocytes which was negatively correlated with patient survival, independent of tumor-node-metastasis classification, tumor grade, and tumor margins.

Chen et al. [81I observed an increase in Treg (CD4 + CD25 + CD127low and FoxP3 mRNA) from peripheral blood of aged healthy controls (60-74 years old) in comparison to young healthy controls (22-56 years old). In addition, Tregs frequency was significantly higher in aged urinary bladder cancer patients (UBC, 62-79 years old) than in aged healthy controls. These authors concluded that upregulated FoxP3 mRNA expression in association with increased Treg frequency could increase tumor escape, immune suppression and lead to ineffective tumor clearance in aged UBC patients.

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