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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Defective γδ T-cell function and granzyme B gene polymorphism in a cohort of newly diagnosed breast cancer patients
Experimental Hematology, Volume 37, No. 7, Year 2009
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Description
Objective: The purpose of this study was to examine the antitumor immune function of γδ 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 γδ T cells in peripheral blood mononuclear cells were assessed by flow cytometry, 51Cr 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 γδ 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 γδ T cells from breast cancer patients produced significantly more interleukin-6 and tumor necrosis factor - α than normal controls. Moreover, ex vivo stimulation of γδ 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 γδ 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 γδ 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 γδ T cells function and granzyme B gene polymorphism in cancers, as well as the potential therapeutic use of zoledronic acid are warranted. © 2009 ISEH - Society for Hematology and Stem Cells.
Authors & Co-Authors
Gaafar, Ameera
Saudi Arabia, Riyadh
Histocompatibility and Immunogenetics
Aljurf, Mahmoud Deeb
Saudi Arabia, Riyadh
King Faisal Heart Institute
Al-Sulaiman, Abdullah
Saudi Arabia, Riyadh
Histocompatibility and Immunogenetics
Iqniebi, Alia
Saudi Arabia, Riyadh
Histocompatibility and Immunogenetics
Manogaran, Pulicat Subramanian
Saudi Arabia, Riyadh
Flow Cytometry
Al-Sayed, Adher Dhaya
Saudi Arabia, Riyadh
King Faisal Heart Institute
Alzahrani, Hazaa
Saudi Arabia, Riyadh
King Faisal Heart Institute
Al-Sharif, Fahad Z.
Saudi Arabia, Riyadh
King Faisal Heart Institute
Al-Mohareb, Fahad I.
Saudi Arabia, Riyadh
King Faisal Heart Institute
Ajarim, Dahish Saeed S.
Saudi Arabia, Riyadh
King Faisal Heart Institute
Tabakhi, Abdelghani
Saudi Arabia, Riyadh
Laboratory Medicine
al-Hussein, Khalid A.F.
Saudi Arabia, Riyadh
Histocompatibility and Immunogenetics
Statistics
Citations: 45
Authors: 12
Affiliations: 5
Identifiers
Doi:
10.1016/j.exphem.2009.04.003
ISSN:
0301472X
Research Areas
Cancer
Genetics And Genomics
Study Design
Cross Sectional Study
Cohort Study