Reduced frequency of NKT-like cells in patients with progressive chronic lymphocytic leukemia

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Abstract
Natural killer T (NKT) cells are a subset of innate immune cells displaying a limited repertoire of antigen specificities and CD1d restriction. Little is known about contribution of NKT cells in cancer initiation and progression. In this study, the frequencies of NKT-like cells, B cells expressing CD1d molecule and CD4+ regulatory (Treg) cells were analyzed in 40 patients with chronic lymphocytic leukemia (CLL) and 15 healthy subjects by flow cytometry. Our results showed that the frequency of CD3+CD56+ NKT-like cells is significantly decreased in progressive (4.9 ± 0.8 % of total CD3+ T cells) compared with indolent (8.1 ± 1.2 %, p = 0.036) patients and healthy subjects (10.6 ± 1.7 %, p = 0.003). However, no association was found between NKT-like cell frequency and immunoglobulin heavy chain variable region gene (IGHV) mutation or CD38 and ZAP70 expression. On the other hand, expression of CD1d molecule was significantly higher in leukemic B cells of patients with CLL (75 ± 1.5 % of total CD19+ B cells) compared to B cells from healthy subjects (59.6 ± 2.2 %, p < 0.001), with no significant difference between progressive and indolent patients. Interestingly, the frequency of Treg cells was inversely correlated with that of NKT-like cells in patients with CLL (r = −0.4, p = 0.002). Our results suggest a protective role for NKT-like cells in patients with CLL, which seems to be downregulated presumably by Treg cells.

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