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Activated CD11b⁺ CD15⁺ Granulocytes Increase in the Blood of Patients with Uveal Melanoma

¹From the Departments of Ophthalmology and ²Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania; and the ³Department of Anatomic Pathology, and the ⁴Department of Ophthalmic Oncology, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio.

PURPOSE. To determine whether activated CD11b⁺ CD15⁺ granulocytes increase in the blood of patients with uveal melanoma.

METHODS. Peripheral blood mononuclear cells (PBMCs) were isolated by density gradient centrifugation from the blood of patients with primary choroidal/ciliochoroidal uveal melanomas (six women, four men; age range, 46–91 years) and healthy control donors (14 women, 10 men; age range, 50–81 years). The expression of CD15 and CD68 on CD11b⁺ myeloid cells within PBMCs and primary uveal melanomas was evaluated by flow cytometry. CD3 chain expression by CD3⁺ T cells in PBMCs and within primary uveal melanomas was measured as an indirect indication of T-cell function.

RESULTS. The percentage of CD11b⁺ cells in PBMCs of patients with uveal melanoma increased 1.8-fold in comparison to healthy donors and comprised three subsets: CD68 negative CD15⁺ granulocytes, which increased 4.1-fold; CD68^– CD15^– cells, which increased threefold; and CD68⁺ CD15^low cells, which were unchanged. A significant (2.7-fold) reduction in CD3 chain expression on CD3⁺ T cells, a marker of T-cell dysfunction, was observed in PBMCs of patients with uveal melanoma in comparison with healthy control subjects and correlated significantly with the percentage of CD11b⁺ cells in PBMCs. CD3 chain expression on T cells within primary tumors was equivalent to CD3 expression in PBMCs of the same patient in four of five patients analyzed.

CONCLUSIONS. Activated CD11b⁺ CD15⁺ granulocytes expand in the blood of patients with uveal melanoma and may contribute to immune evasion by ocular tumors by inhibiting T-cell function via decreasing CD3 chain expression.

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