Untreated stage IV melanoma patients exhibit abnormal monocyte phenotypes and decreased functional capacity

Rahul Chavan, Daniela Salvador, Michael Gustafson, Allan B Dietz, Wendy Nevala, Svetomir Nenad Markovic

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Monocytes may contribute to tumor progression in part by mediating tumor-induced immunosuppression. Alterations to the monocyte populations and functions in untreated patients with late-stage melanoma are not fully understood. To characterize these alterations, we compared the frequency, phenotype, and functional capacity of peripheral blood monocytes and other myeloid cells in untreated, newly diagnosed stage IV melanoma patients (n = 18) with those in healthy volunteers. Stage IV untreated melanoma patients exhibited a sizeable decrease in the percentage of monocytes (P < 0.0001) that included a drop in the percentage of the CD14(+)CD16(-) classical monocyte pool (P = 0.006). Although there was not a significant difference in the CD14(+)HLA-DR(low/-) monocyte population between the patients with melanoma and the healthy volunteers, the HLA-DR levels were considerably lower in the patients' CD14(+)CD16(+) intermediate (P < 0.0001) and CD14(low)CD16(+) nonclassical monocyte populations (P = 0.001). Decreased surface expression of CD86 (P = 0.0006) and TNFRII (P = 0.0001) and increased expression of tissue factor and PD-L1 (P = 0.003) were identified on monocytes from patients with melanoma. Furthermore, these monocytes had decreased ability to upregulate CD80 expression and cytokine production following stimulation with agonist of Toll-like receptor 3 (TLR3). Peripheral blood dendritic cell subsets were decreased in untreated stage IV melanoma patients. Our study demonstrates that untreated late-stage melanoma patients exhibit monocytopenia in addition to phenotypic and functional deficiencies that may negatively affect their immune function. These findings open new avenues into examining the role of monocyte populations in melanoma development.

Original languageEnglish (US)
Pages (from-to)241-248
Number of pages8
JournalCancer immunology research
Volume2
Issue number3
DOIs
StatePublished - Mar 1 2014

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Monocytes
Melanoma
Phenotype
HLA-DR Antigens
Population
Healthy Volunteers
Toll-Like Receptor 3
Thromboplastin
Myeloid Cells
Immunosuppression
Dendritic Cells
Blood Cells
Neoplasms
Up-Regulation
Cytokines

ASJC Scopus subject areas

  • Medicine(all)

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Untreated stage IV melanoma patients exhibit abnormal monocyte phenotypes and decreased functional capacity. / Chavan, Rahul; Salvador, Daniela; Gustafson, Michael; Dietz, Allan B; Nevala, Wendy; Markovic, Svetomir Nenad.

In: Cancer immunology research, Vol. 2, No. 3, 01.03.2014, p. 241-248.

Research output: Contribution to journalArticle

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