Defective γδ T-cell function and granzyme B gene polymorphism in a cohort of newly diagnosed breast cancer patients

Objective. The purpose of this study was to examine the antitumor immune function of gamma delta T cells and to scan the granzyme B gene for the known single nucleotide polymorphism in breast cancer patients and normal controls. Materials and Methods. Levels, cytotoxicity, and functional capacity of gamma delta T cells in peripheral blood mononuclear cells were assessed by How cytometry, Cr-51 release, and ELISpot assays, respectively. Furthermore, sequence based typing was adopted to screen for granzyme B gene polymorphism. Results. We have found that the frequency and function of gamma delta T cells are reduced both in peripheral blood mononuclear cells of 30 newly diagnosed breast cancer patients (2 [1.2, 3]), compared with 38 normal controls (3.2 [2.5, 5.7]) (p = 0.02). In addition, resting gamma delta T cells from breast cancer patients produced significantly more interleukin-6 and tumor necrosis factor - alpha than normal controls. Moreover, ex vivo stimulation of gamma delta T cells with zoledronic acid and interleukin-2 compensated in part for this deficiency, as it stimulated the proliferation, cytokine production, and enhanced the expression of messenger RNA of granzyme B. Interestingly, when the known granzyme B gene polymorphism was screened, we found the prevalence of the mutated genotype RAH/RAH to be significantly (p < 0.017) associated with breast cancer patients (14.30%) compared with normal donors (1.40%). Cytotoxicity exerted by gamma delta T cells on Daudi and MCF-7 was significantly higher in donors with the wild-type QPY/QPY (50%) compared with donors with RAH/RAH (21%). Conclusions. Our data suggest that reduction in the proportion of gamma delta T cells and granzyme B gene polymorphism leads to defective immune function in breast cancer patients. Treatment with zoledronic acid amend partially this fault. Further studies of gamma delta T cells function and granzyme B gene polymorphism in cancers, as well as the potential therapeutic use of zoledronic acid are warranted. (C) 2009 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.