CD4+CD25+ regulatory T cells in patients with gastrointestinal malignancies: possible involvement of regulatory T cells in disease progression.
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TLDR
The purpose of the current study was to demonstrate the possible involvement of CD4+CD25+ regulatory T cells in immune system impairment in patients with gastrointestinal malignancies.Abstract:
BACKGROUND
Active suppression by CD4+CD25+ regulatory T cells plays an important role in the down-regulation of the response of T cells to foreign and self antigens. Experimental tumor models in mice revealed that regulatory T cells inhibit antitumor immune responses. The purpose of the current study was to demonstrate the possible involvement of CD4+CD25+ regulatory T cells in immune system impairment in patients with gastrointestinal malignancies.
METHODS
The phenotypes of lymphocytes, particularly those of CD4+CD25+ T cells, were analyzed in peripheral blood in 149 patients with gastrointestinal malignancies and in ascites in 7 patients with peritoneal dissemination. In addition, cytokine production after in vitro stimulation was examined in CD4+CD25+ and CD4+CD25− T cells isolated from patients with malignant disease.
RESULTS
Compared with healthy volunteers, patients with gastrointestinal malignancies had a higher proportion of CD4+CD25+ T cells in peripheral blood, due to the presence of a drastically smaller number of CD4+CD25− T cells. Among patients with gastric carcinoma, those with higher percentages of CD4+CD25+ T cells had a poorer prognosis than did those with lower percentages. CD4+CD25+ T cells also were present in greater proportions in ascites from patients who had advanced-stage disease with peritoneal dissemination. Isolated CD4+CD25+ T cells from patients with malignant disease produced interleukin (IL)-4 and IL-10 but not IL-2 or interferon-γ; these cells also inhibited cytokine production by CD4+CD25− T cells after in vitro stimulation.
CONCLUSIONS
The relative increase in CD4+CD25+ regulatory T cells may be related to immunosuppression and tumor progression in patients with gastrointestinal malignancies. This finding suggests that the use of immunomodulatory therapy to treat patients with gastrointestinal malignancies may be an effective strategy. Cancer 2003;98:1089–99. © 2003 American Cancer Society.
DOI 10.1002/cncr.11618read more
Citations
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TL;DR: A role for T reg cells in blunting the NK cell arm of the innate immune system is supported in controlling innate antitumor immunity through inhibition of NK cell effector functions and down-regulated NKG2D receptors on theNK cell surface.
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References
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TL;DR: It is shown that chronic activation of both human and murine CD4+T cells in the presence of interleukin (IL)-10 gives rise to CD4-T-cell clones with low proliferative capacity, producing high levels ofIL-10, low levels of IL-2 and no IL-4.
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