Exogenous IL-2 Induces FoxP3+ Th17 Cells In Vivo in Melanoma Patients.
Exogenous IL-2 Induces FoxP3+ Th17 Cells In Vivo in Melanoma Patients.
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DOI：
10.1097/cji.0000000000000139
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Ford ML
中科院分区：
文献类型：
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作者：
Diller ML;Kudchadkar RR;Delman KA;Lawson DH;Ford ML
Th17 cells represent a distinct subset of CD4+ effector T cells with potent pathogenic qualities, capable of directly mediating tumor cell destruction. IL-2 has frequently been shown to have a negative impact on Th17 differentiation while supporting regulatory T cell (FoxP3+CD4+, TREG) growth and development in both in vitro models and in vivo animal models. We investigated the effect of in vivo IL-2 on both the Th17 and FoxP3+CD4+ T cell compartments in a human model of cancer. High-dose IL-2 (HDIL-2) was administered at a dose of 720,000 IU/kg to patients with melanoma (n=7) and peripheral blood was collected at baseline and at 24, 48, 72, and 96 hours post-treatment. PBMCs were isolated and underwent intracellular cytokine and extracellular receptor staining for flow cytometry. We report that HDIL-2 increased both frequencies and absolute numbers of Th17 cells on day 4 of treatment. The administration of HDIL-2 to patients with melanoma increased IL-6 production by peripheral immune cells, a cytokine vital in the downregulation of FoxP3 expression and expansion of the Th17 cell population. Furthermore, we demonstrated that FoxP3+CD4+ T cells express IL-17 in patients with melanoma undergoing HDIL-2 therapy. Taken together, our findings indicate that HDIL-2 combined with the conditions of malignancy create an immune environment supportive of Th17 differentiation and that expansion of this compartment may occur via the trans-differentiation of IL-17-secreting FoxP3+CD4+ T cells.
