title: Combining FoxP3 and Helios with GARP/LAP markers can identify expanded Treg subsets in cancer patients.
abstract: 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 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. 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.
authors.affiliation: Biomedical Research Centre, School of Environment and Life Sciences, University of Salford, Manchester, United Kingdom.|College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
authors.forename: May
authors.initials: M
authors.lastname: Abd Al Samid
authors.affiliation: Biomedical Research Centre, School of Environment and Life Sciences, University of Salford, Manchester, United Kingdom.
authors.forename: Belal
authors.initials: B
authors.lastname: Chaudhary
authors.affiliation: Institute of Cancer Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Yazan S
authors.initials: YS
authors.lastname: Khaled
authors.affiliation: Institute of Cancer Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Basil J
authors.initials: BJ
authors.lastname: Ammori
authors.affiliation: Biomedical Research Centre, School of Environment and Life Sciences, University of Salford, Manchester, United Kingdom.|College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.|Institute of Cancer Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Eyad
authors.initials: E
authors.lastname: Elkord
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000378:metabolism; D050883:HSC70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D051740:Ikaros Transcription Factor / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008113:Liver Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000556:secondary; D008213:Lymphocyte Activation; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D050883:HSC70 Heat-Shock Proteins; C494371:HSPA8 protein, human; C111431:IKZF2 protein, human; C508609:IL10 protein, human; C087215:LRRC32 protein, human; D008565:Membrane Proteins; D016753:Interleukin-10; D051740:Ikaros Transcription Factor
keywords: FoxP3; GARP/LAP; Helios; markers; regulatory T cells