Perturbations of both nonregulatory and regulatory FOXP3+ T cells in patients with malignant melanoma

Abstract

These findings demonstrate that patients with melanoma have distinct and differential perturbation of both regulatory and nonregulatory FOXP3+ T cells. The degree of perturbation is associated with tumour burden and progression, suggesting that the perturbation reflects fundamental pathophysiological processes in patients with melanoma. The presented analysis provides a practical approach to investigate the immunological environment of cancer patients.

Convergences and Divergences of Thymus- and Peripherally Derived Regulatory T Cells in Cancer

“…The tumor context, which conceivably belongs to the latter category, should be characterized by aT reg expansion. In line with this hypothesis, CD45RO + FOXP3 high aT reg were found significantly expanded in the peripheral blood, and much more at the tumor site, in patients with malignant melanoma (118). Also the non-T reg and the rT reg fractions were increased, but only in the peripheral blood, in cancer patients compared to healthy controls, and both subsets positively correlated with tumor progression (118).…”

“…In line with this hypothesis, CD45RO + FOXP3 high aT reg were found significantly expanded in the peripheral blood, and much more at the tumor site, in patients with malignant melanoma (118). Also the non-T reg and the rT reg fractions were increased, but only in the peripheral blood, in cancer patients compared to healthy controls, and both subsets positively correlated with tumor progression (118). The non-T reg pool produced some IFN-γ and its frequency returned to normal levels after tumor removal, thus probably representing aberrantly activated T conv , or T reg with attenuated FOXP3 activity (118).…”

“…Also the non-T reg and the rT reg fractions were increased, but only in the peripheral blood, in cancer patients compared to healthy controls, and both subsets positively correlated with tumor progression (118). The non-T reg pool produced some IFN-γ and its frequency returned to normal levels after tumor removal, thus probably representing aberrantly activated T conv , or T reg with attenuated FOXP3 activity (118). A much deeper knowledge on T reg dynamics in cancer is needed to better understand the role played by each specialized component in suppressing anti-tumor type-1, or pro-tumor inflammatory, responses.…”

“…In line with this possibility, TAA-specific T conv , but not TAA-specific T reg , produced IFN-γ in patients with epithelial ovarian cancer (99). In both healthy subjects (117) and malignant melanoma patients (118), IFN-γ-producing cells were enriched within the circulating CD45RA − FOXP3 low (CD45RO + ) non-T reg subset, mostly including activated T conv and/or uncommitted T reg . Conversely, in ovarian cancer, tumor-infiltrating T reg were enriched in CXCR3 + cells, highly expressing T-bet but poorly producing IFN-γ, and strongly suppressing Th1 response ex vivo (157).…”

Comparison of Foxp3+ Regulatory T cells and CD163+ Macrophages in Invasive and Non-invasive Extramammary Paget’s Disease

“…This discrepancy may be related to the facts that the expression of Foxp3 is induced in all CD4 T cells by antigenic stimulation (23), that the Foxp3* CD4 T-cell fraction includes effector cytokine-producing, non-regulatory T cells (24), and that these non-regulatory Foxp3''""-' T cells are most probably effector T cells (25). Indeed, although we calculated the expression of Foxp3 only in highly expressed cells, the manual counting of immunoreactive cells may be a limitation of data collection in our study.…”