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

Oncotarget
May Abd Al SamidEyad Elkord

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...Continue Reading

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Citations

Feb 13, 2020·Clinical and Experimental Pharmacology & Physiology·Li NiuBo Hu
Oct 1, 2017·Clinical and Experimental Immunology·S M ToorE Elkord
Jun 7, 2018·Journal for Immunotherapy of Cancer·Tolga TuranJosue Samayoa
May 23, 2019·Journal for Immunotherapy of Cancer·Davide BedognettiUNKNOWN Society for Immunotherapy of Cancer (SITC) Cancer Immune Responsiveness Task Force and Working Groups
May 2, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Zhuqing LiuRobert L Ferris
Dec 28, 2019·Seminars in Cell & Developmental Biology·Monika Lodyga, Boris Hinz
Dec 12, 2017·Emerging Topics in Life Sciences·Rongze LuFrancesco M Marincola
Jun 21, 2021·Molecular Medicine·Xiguang YeZhiwen Zhang

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Methods Mentioned

BETA
blood collection
density gradient centrifugation
flow cytometry

Software Mentioned

FlowJo
GraphPad
Helios
GraphPad Prism

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