Activated CD11b+ CD15+ granulocytes increase in the blood of patients with uveal melanoma.
OBJECTIVE
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. CD3zeta chain expression by CD3epsilon(+) 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 CD3zeta chain expression on CD3epsilon(+) 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. CD3zeta chain expression on T cells within primary tumors was equivalent to CD3zeta 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 CD3zeta chain expression.
Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA. mckennakc@upmc.edu
Kyle C
KC
McKenna
Kelly M
KM
Beatty
Richard A
RA
Bilonick
Lynn
L
Schoenfield
Kira L
KL
Lathrop
Arun D
AD
Singh
D000368:Aged; D000369:Aged, 80 and over; D001918:Brachytherapy; D039481:CD11b Antigen / Q000378:metabolism*; D017252:CD3 Complex / Q000378:metabolism; D002499:Centrifugation, Density Gradient; D015353:Eye Enucleation; D005260:Female; D005434:Flow Cytometry; D006098:Granulocytes / Q000276:immunology*; D006801:Humans; D007124:Immunoenzyme Techniques; D016256:Lewis X Antigen / Q000378:metabolism*; D008213:Lymphocyte Activation; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000628:therapy; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*; D014604:Uveal Neoplasms / Q000097:blood* / Q000628:therapy
D039481:CD11b Antigen; D017252:CD3 Complex; C115335:CD3E protein, human; C509295:ITGAM protein, human; D016256:Lewis X Antigen