The Dysfunction of NK Cells in Patients with Type 2 Diabetes and Colon Cancer
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ORIGINAL ARTICLE
The Dysfunction of NK Cells in Patients with Type 2 Diabetes and Colon Cancer Paweł Pia˛tkiewicz • Tomasz Miłek • Małgorzata Bernat-Karpin´ska • Monika Ohams Anna Czech • Piotr Ciostek
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Received: 6 July 2012 / Accepted: 13 February 2013 / Published online: 2 March 2013 L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2013
Abstract Glucose metabolism disorders influence anticarcinogenic function of natural killer (NK) cells. The aim of this study was to evaluate the number and cytotoxic activity of NK cells in type 2 diabetic (T2D) patients with negative family history of cancer, type 2 diabetic subjects with newly diagnosed untreated colon cancer (T2DCC) and patients without type 2 diabetes with newly diagnosed, untreated colon cancer (CC). Incubation tests were performed in 18 T2D patients, treated with diet and oral antidiabetic agents, 16 T2DCC; cT1-4N0M0 (c-clinical diagnosis based on computed tomography, colonoscopy and histopathology) treated with diet and oral antidiabetic agents and 16 normoglycemic CC; cT1-4N0M0. Control group included 18 metabolically healthy (with normal fasting glucose and normal glucose tolerance) subjects (HS) with negative family history of cancer, matched by age, BMI and waist circumference. Peripheral blood mononuclear cells were isolated by means of gradient centrifugation. The K562 human erythroleukemia cell line served as the standard target for human NK cytotoxicity assay. The T2D revealed an increased number of NK cells (13.56 ± 5.9 vs 9.50 ± 4.8 %; p \ 0.05) when compared
P. Pia˛tkiewicz (&) M. Bernat-Karpin´ska A. Czech Chair and Department of Internal Diseases and Diabetology, Medical University of Warsaw, Warsaw, Poland e-mail: [email protected] T. Miłek P. Ciostek Chair and Department of General and Vascular Surgery, Medical University of Warsaw, Warsaw, Poland M. Ohams Department of Clinical Immunology, Medical University of Warsaw, Warsaw, Poland
with HS, yet these cells had a decreased activity (3.3 ± 2.5 vs 9.4 ± 3.6 %; p \ 0.01). The CC demonstrated a decreased activity (2.9 ± 1.8 %; p \ 0.01) but a similar number (8.82 ± 3.7 %; not significant) of NK cells when compared to HS. The T2DCC NK cells were characterized by trace cytotoxic activity (1.1 ± 0.7 %; p \ 0.01) and nearly three times greater amount (21.24 ± 7.5 %; p \ 0.01) when compared to T2D. Type 2 diabetes and CC are associated with disadvantageous alterations of NK cells, leading to impairment in their cytotoxic activity. The impaired activity of NK cells in T2D can be involved in the increased carcinogenic risk and can promote a higher incidence of CC. Keywords
NK cells Diabetes Colon cancer
Introduction Natural killer (NK) cells constitute from 5 to 19 % of the peripheral blood lymphocytes, and most of them have morphology of a large granular lymphocyte (Hannet et al. 1992; Timonen et al. 1981). They are characterized by the ability to destroy target cells spontaneously, without prior immunization, and their cytotoxic effect is not subject
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