Research Papers:

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

May Abd Al Samid, Belal Chaudhary, Yazan S. Khaled, Basil J. Ammori and Eyad Elkord _

PDF  |  HTML  |  How to cite

Oncotarget. 2016; 7:14083-14094. https://doi.org/10.18632/oncotarget.7334

Metrics: PDF 2236 views  |   HTML 2853 views  |   ?  


May Abd Al Samid1,2,*, Belal Chaudhary1,*, Yazan S. Khaled3, Basil J. Ammori3, Eyad Elkord1,2,3

1Biomedical Research Centre, School of Environment and Life Sciences, University of Salford, Manchester, United Kingdom

2College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates

3Institute of Cancer Sciences, University of Manchester, Manchester, United Kingdom

*These authors contributed equally to this work

Correspondence to:

Eyad Elkord, e-mail: [email protected], [email protected] and [email protected]

Keywords: regulatory T cells, markers, GARP/LAP, FoxP3, Helios

Received: December 09, 2015     Accepted: January 29, 2016     Published: February 11, 2016


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. 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. 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. Additionally, GARP–/+LAP+ CD4+ T cells made IL-10, and not IFN-γ, and levels of IL-10-secreting CD4+ T cells were elevated in LICRC patients, especially with higher tumor staging. Taken together, our results indicate that 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.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 7334