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  • Open Access

High Th17:Treg ratio may predict complete response to HDIL-2 in the setting of melanoma

  • 1,
  • 2,
  • 3 and
  • 3
Journal for ImmunoTherapy of Cancer20153 (Suppl 2) :P297

https://doi.org/10.1186/2051-1426-3-S2-P297

  • Published:

Keywords

  • Melanoma
  • Th17 Cell
  • TREG Cell
  • Paired Student
  • Subsequent Cycle

Introduction

In vitro and in vivo experiments have demonstrated a potent yet opposite effect of IL-2 on both regulatory T cells (TREG) and IL-17+CD45RA-CD4+ T cells (Th17). TREG cells have been implicated as an important immunoregulator enhancing tumor growth whereas Th17 cells may mediate tumor destruction. This study compares the effect of high-dose IL-2 (HDIL-2) on both the TREG and Th17 compartments in responders and non-responders.

Methods

Peripheral blood was collected at baseline and at 24, 48, 72, and 96 hours post-treatment from 6 patients undergoing HDIL-2 therapy under an IRB approved protocol. No patients enrolled received anti-PD-1 or anti-CTLA4 therapies. PBMCs were isolated and underwent intracellular cytokine and extracellular receptor staining for flow cytometry. Statistical analysis was performed using paired student's t tests via Prism 6.0e software.

Results

5 of 6 patients clinically progressed on HDIL-2 therapy (non-responders, NR), and these patients demonstrated an increase in the frequency of CD25+FoxP3+CD4+ T cells (TREG) on day 4 of treatment (4% +/- 1% on day 0 to 14% +/- 6% on day 4, p value = 0.06). A single patient responded to HDIL-2 therapy (complete responder, CR) and demonstrated a decrease in the frequency of TREG cells on day 4 of treatment (9% on day 0 to 7% on day 4). HDIL-2 increased the frequency of IL-17+CD45RA-CD4+ T cells (Th17) on day 4 of therapy in all patients analyzed (0.7% +/- 0.4% on day 0 versus 2% +/- 1% on day 4, p value=0.04; Figure 1). Absolute numbers of Th17 cells also demonstrated a statistically significant increase on day 4 of therapy (5 +/- 1 cell/µL on day 0 versus 38 +/- 24 cells/µL on day 4, p value=0.04, Figure 2). Subsequent analyses demonstrated a negative Th17:TREG ratio on day 4 of HDIL-2 treatment in all non-responders. Importantly, the complete responder demonstrated a positive Th17:TREG ratio on day 4 of treatment (Figure 3). The observed difference in cytokine production appeared to be specific to IL-17 as there was no statistically significant change in frequency or total numbers of IFN-g+ or IL-2+CD4+ and CD8+ T cells.

Conclusion

Our results suggest a distinct immunophenotype indicative of response to HDIL-2. Analysis of peripheral TREG and Th17 cell frequencies early in the course of HDIL-2 therapy may help identify those patients who would benefit from subsequent cycles.

Authors’ Affiliations

(1)
Department of General Surgery, Emory University, Atlanta, GA, USA
(2)
Emory University Transplant Center, Atlanta, GA, USA
(3)
Emory University Winship Cancer Institute, Atlanta, GA, USA

Copyright

© Diller et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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