Combining FoxP3 and Helios with GARP/LAP markers to identify expanded Treg subsets in cancer patients

Elkord, E; Abd Al Samid, M; Chaudhary, B; Khaled, Y; Ammori, B

Abstract

Background: Regulatory T cells (Tregs) comprise numerous heterogeneous subsets with distinct phenotypic and functional features. Identifying Treg markers is critical to investigate the role and clinical impact of various Treg subsets in pathological settings, and also for developing more effective immunotherapies. Methods: We investigated different Treg subsets as defined by expression of FoxP3 and Helios transcription factors and GARP and LAP immunosuppressive markers in peripheral blood samples isolated from patients with pancreatic cancer (PC) and liver metastases from colorectal cancer (LICRC), and compared their levels to control groups. Results: We have recently shown that non-activated FoxP3–Helios+ and activated FoxP3+/–Helios+ CD4+ T cells express GARP/LAP immunosuppressive markers in healthy donors. In this study, we report similar observations in the peripheral blood of patients with pancreatic cancer (PC) and liver metastases from colorectal cancer (LICRC). Comparing levels of different Treg subpopulations in cancer patients and controls, we report that in PC patients, and unlike LICRC patients, there was no increase in Treg levels as defined by FoxP3 and Helios. However, defining Tregs based on GARP/LAP expression showed that FoxP3–LAP+Tregs in non-activated and activated settings, and FoxP3+Helios+GARP+LAP+activated Tregs were significantly increased in both groups of patients, compared with controls. Additionally, GARP–/+LAP+ CD4+ T cells made IL-10, and not IFN-g, and levels of IL-10-secreting CD4+ T cells were elevated in LICRC patients, especially with higher tumor staging. Conclusions: This work implies that a combination of Treg-specific markers could be used to more accurately determine expanded Treg subsets and to understand their contribution in cancer settings, and investigations of Treg levels in different cancers should consider diverse Treg-related markers such as GARP, LAP, Helios, and others and not only FoxP3 as a sole Treg-specific marker.

Citation

Elkord, E., Abd Al Samid, M., Chaudhary, B., Khaled, Y., & Ammori, B. (2016). Combining FoxP3 and Helios with GARP/LAP markers to identify expanded Treg subsets in cancer patients. Journal of Clinical Oncology, 34(15_sup), e23118. https://doi.org/10.1200/jco.2016.34.15_suppl.e23118

• Journal Article Type: Article
• Publication Date: May 20, 2016
• Deposit Date: Sep 17, 2018
• Journal: Journal of Clinical Oncology
• Print ISSN: 0732-183X
• Publisher: American Society of Clinical Oncology
• Volume: 34
• Issue: 15_sup
• Pages: e23118
• DOI: https://doi.org/10.1200/jco.2016.34.15_suppl.e23118
• Keywords: Cancer Research, Oncology
• Publisher URL: https://doi.org/10.1200/jco.2016.34.15_suppl.e23118
• Related Public URLs: http://ascopubs.org/journal/jco