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 and 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.

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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 FoxP3Helios+ 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 FoxP3LAP+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.

Item Type: Article
Uncontrolled Keywords: Cancer Research, Oncology
Schools: Schools > School of Health Sciences
Journal or Publication Title: Journal of Clinical Oncology
Publisher: American Society of Clinical Oncology (ASCO)
ISSN: 1527-7755
Related URLs:
SWORD Depositor: Publications Router
Depositing User: Publications Router
Date Deposited: 17 Sep 2018 08:59
Last Modified: 17 Sep 2018 08:59
URI: http://usir.salford.ac.uk/id/eprint/48367

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