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Mandapathil M, Szczepanski M, Harasymczuk M, et al. CD26 expression and adenosine deaminase activity in regulatory T cells (Treg) and CD4(+) T effector cells in patients with head and neck squamous cell carcinoma. Oncoimmunology. 2012;1(5):659-669doi: 10.4161/onci.20387.
Mandapathil, M., Szczepanski, M., Harasymczuk, M., Ren, J., Cheng, D., Jackson, E. K., Gorelik, E., Johnson, J., Lang, S., & Whiteside, T. L. (2012). CD26 expression and adenosine deaminase activity in regulatory T cells (Treg) and CD4(+) T effector cells in patients with head and neck squamous cell carcinoma. Oncoimmunology, 1(5), 659-669. https://doi.org/10.4161/onci.20387
Mandapathil, Magis, et al. "CD26 expression and adenosine deaminase activity in regulatory T cells (Treg) and CD4(+) T effector cells in patients with head and neck squamous cell carcinoma." Oncoimmunology vol. 1,5 (2012): 659-669. doi: https://doi.org/10.4161/onci.20387
Mandapathil M, Szczepanski M, Harasymczuk M, Ren J, Cheng D, Jackson EK, Gorelik E, Johnson J, Lang S, Whiteside TL. CD26 expression and adenosine deaminase activity in regulatory T cells (Treg) and CD4(+) T effector cells in patients with head and neck squamous cell carcinoma. Oncoimmunology. 2012 Aug 01;1(5):659-669. doi: 10.4161/onci.20387. PMID: 22934258; PMCID: PMC3429570.
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Oncoimmunology. 2012 Aug 01;1(5):659-669. doi: 10.4161/onci.20387.

CD26 expression and adenosine deaminase activity in regulatory T cells (Treg) and CD4(+) T effector cells in patients with head and neck squamous cell carcinoma.

Oncoimmunology

Magis Mandapathil, Miroslaw Szczepanski, Malgorzata Harasymczuk, Jin Ren, Dongmei Cheng, Edwin K Jackson, Elieser Gorelik, Jonas Johnson, Stephan Lang, Theresa L Whiteside

Affiliations

  1. University of Pittsburgh Cancer Institute; Pittsburgh, PA USA ; Department of Otorhinolaryngology; University of Duisburg-Essen; Essen, Germany.

PMID: 22934258 PMCID: PMC3429570 DOI: 10.4161/onci.20387

Abstract

Adenosine deaminase (ADA) is responsible for the deamination of immunosuppressive adenosine to inosine. In human T lymphocytes, ADA is associated with dipeptidyl peptidase IV (CD26). ADA expression and activity were evaluated in regulatory T cells (Treg) and CD4(+) T effector cells (Teff) of patients with head and neck squamous cell cancer (HNSCC). CD4(+)CD39(+) and CD4(+)CD39(neg) T cells were isolated by single-cell sorting from the peripheral blood of 15 HNSCC patients and 15 healthy donors (NC). CD26/ADA expression in these cells was studied by multicolor flow cytometry, confocal microscopy, RT-PCR and immunohistochemistry in tumor tissues. ADA activity was evaluated by mass spectrometry, suppression of Teff proliferation in CFSE assays and cytokine production by Luminex. CD4(+)CD39(+) Treg had low and CD4(+)CD39(neg) Teff high CD26/ADA expression and ADA activity in NC or HNSCC. The frequency and suppressor activity of CD39(+)CD26(neg) Treg were elevated in patients relative to NC (p < 0.01). However, ADA activity in patients' CD4(+)CD39(neg) Teff was decreased (p < 0.05), resulting in extracellular adenosine accumulation. Also, patients' Teff were more sensitive to inhibitory signals delivered via adenosine receptors. IL-2, IL12 and INFγ upregulated ADA expression and activity in CD4(+)CD39(neg) Teff, whereas IL-10, PGE(2) and CADO downregulated it. The differentially expressed CD26/ADA can serve as surface markers for functionally-active CD39(+)CD26(neg) Treg.

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