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. 2014 Apr;58(2):182-6.
doi: 10.1016/j.molimm.2013.11.018. Epub 2013 Dec 25.

Circulating immune cell and microRNA in patients with uveal melanoma developing metastatic disease

Susan Achberger  1 , Wayne Aldrich  1 , Raymond Tubbs  2 , John W Crabb  3 , Arun D Singh  3 , Pierre L Triozzi  4
Affiliations

Circulating immune cell and microRNA in patients with uveal melanoma developing metastatic disease

Susan Achberger et al. Mol Immunol. 2014 Apr.

Abstract

Background: The immune response has been implicated in the control of uveal melanoma progression. Epigenetic mechanisms mediated by specific microRNAs (miRs) regulate immune responses.

Methods: Blood was drawn from six patients with uveal melanoma followed from diagnosis, at which time there was no clinical or radiographic evidence of metastasis, until metastasis manifested. Circulating T cell, natural killer (NK), natural killer T (NKT), and myeloid suppressor cell populations were assessed by flow cytometry. CD3(+), CD15(+), and CD56(+) cells were isolated using immunomagnetic beads. Plasma and cellular levels of immune regulatory miRs were determined by quantitative polymerase chain reaction assays.

Results: The development of metastasis was associated with decreases in circulating CD3(-)CD56(dim) NK cells and CD8(+) and double-negative CD3(+)CD56(+) NKT cells. ICOS(+)CD4(+)FoxP3(+) T regulatory cells and CD11b(+)CD14(-)CD15(+) myeloid suppressor cells increased. Plasma levels of miR-20a, 125b, 146a, 155, 181a, and 223 were higher in the study patients at diagnosis compared to controls. Plasma levels of miR-20a, 125b, 146a, 155, and 223 increased, and miR-181a decreased when metastasis manifested. Alterations in immune regulatory miRs were also observed in CD3(+), CD15(+), and CD56(+) cell populations.

Conclusions: The development of metastasis in uveal melanoma is associated with changes in immune effector and regulatory cells consistent with lessening tumor immune surveillance. These changes are associated with changes in plasma and cellular levels of immune regulatory miRs. The results may help guide uveal melanoma immunotherapy and biomarker development.

Keywords: Biomarkers; Immune response; MicroRNA; Uveal melanoma.

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Figures

Fig. 1
Fig. 1
(A) T cell populations and (B) T cell receptor ζ chain expression at diagnosis (P) and at metastasis (M) (n = 6).
Fig. 2
Fig. 2
(A) NK and (B) NKT populations at diagnosis (P) and at metastasis (M) (n = 6).
Fig. 3
Fig. 3
(A) Treg cell, (B) ICOS+ Treg cell, and MDSC at diagnosis (P) and at metastasis (M) (n = 6).
Fig. 4
Fig. 4
Plasma levels of healthy donor controls (n = 26) and of uveal melanoma patients (n = 6) at primary diagnosis and at metastasis. *P < 0.05 compared to primary and metastasis; **P < 0.05 compared to primary.
Fig. 5
Fig. 5
Immune miR levels of CD3, CD15, and CD56 peripheral blood cells at diagnosis (P) and at metastasis (M) (n = 5).
See this image and copyright information in PMC

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