Complete response to high-dose IL-2 and enhanced IFNγ+Th17 : TREG ratio in a melanoma patient.
Complete response to high-dose IL-2 and enhanced IFNγ+Th17 : TREG ratio in a melanoma patient.
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DOI：
10.1097/cmr.0000000000000283
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发表时间：
2016-10
影响因子：
2.2
通讯作者：
Ford ML
中科院分区：
文献类型：
--
作者：
Diller ML;Kudchadkar RR;Delman KA;Lawson DH;Ford ML
High dose IL-2 (HDIL-2) is associated with complete and durable responses in only 5–10% of patients with stage IV melanoma and the toxicity profile is significant. In vivo human models have recently demonstrated a stimulatory effect of exogenous IL-2 on both the Th17 and regulatory T cell (TREG) compartments. We investigated and compared the effect of HDIL-2 on the Th17 and TREG compartments in HDIL-2 responders versus non-responders. High-dose IL-2 (HDIL-2) was administered at a dose of 720,000 IU/kg to patients with melanoma (n=6) and peripheral blood was collected at baseline and at 24, 48, 72, and 96 hours during treatment. PBMCs were isolated and underwent intracellular cytokine and extracellular receptor staining for flow cytometry. 5 of 6 patients clinically progressed on HDIL-2 therapy, and these patients demonstrated an increase in the frequency of regulatory T cells on day 4 of treatment. A single patient responded to HDIL-2 therapy and demonstrated a decrease in the frequency of TREG cells on day 4 of treatment. We found that HDIL-2 resulted in a larger increase in the frequency of IFNγ+Th17 cells in the responder when compared to all non-responders. As such, all non-responders demonstrated a negative IFNγ+Th17:TREG ratio, whereas the complete responder demonstrated a positive IFNγ+Th17:TREG ratio. Our results suggest a distinct immunophenotype may be associated with response to HDIL-2. The peripheral Th17:TREG ratio may serve as an early biomarker in the setting of HDIL-2 to help identify those patients who would benefit from subsequent cycles.
