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K. C. McKenna, K. M. Beatty, R. A. Bilonick, A. D. Singh; Activated CD11b+ CD15+ Granulocytes Increase in Blood of Uveal Melanoma Patients. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3392.
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To determine whether activated CD11b+ CD15+ granulocytes are increased in the blood of uveal melanoma patients.
Peripheral blood mononuclear cells (PBMC) were isolated by density gradient centrifugation from the blood of patients with primary choroidal/ciliochoroidal uveal melanomas (6 female, 4 male, aged 46-91 years) and healthy control donors (14 female, 10 male, aged 50-81 years). The expression of CD15 and CD68 on CD11b+ myeloid cells within PBMC and primary uveal melanomas was evaluated by flow cytometric analysis. CD3ζ chain expression by CD3ε+ T cells in PBMC and within primary uveal melanomas was measured as an indirect measure of T cell function.
The percentage of CD11b+ cells in PBMC of uveal melanoma patients increased 1.8-fold in comparison to healthy donors and was comprised of three subsets: CD68 negative CD15+ granulocytes which increased 4.1-fold, CD68- CD15- cells which increased 3-fold and CD68+ CD15 low cells which were unchanged. A significant 2.7-fold reduction in CD3ζ chain expression on CD3ε+ T cells, a marker of T cell dysfunction, was observed in PBMC of uveal melanoma patients in comparison to healthy controls and was significantly correlated with the percentage of CD11b+ cells in PBMC. CD3ζ chain expression on T cells within primary tumors was equivalent to CD3ζ expression in PBMC of the same patient in four of five patients analyzed.
CD11b+ CD15+ granulocytes expand in the blood of uveal melanoma patients and may contribute to immune evasion by ocular tumors by inhibiting T cell function via decreasing CD3ζ chain expression.
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