Monocytes may contribute to tumor progression in part by mediating tumor-induced immunosuppression. Alterations to the monocyte populations and functions in untreated late stage melanoma patients are not fully understood. To characterize the frequency, phenotype, and functional capacity of peripheral blood monocytes and other myeloid cells in untreated, newly diagnosed stage IV melanoma patients (n= 18) were compared to that of monocytes and myeloid cells from healthy volunteers. Stage IV untreated melanoma patients exhibited a sizeable decrease in the percentage of monocytes (p<0.0001) in comparison to healthy volunteers. We further analyzed the monocyte compartments and found that these patients also had a drop in the percentage of CD14+CD16- classical monocytes pool (p=0.006). Although we did not see a significant difference in the CD14+HLA-DRlow/- monocyte population from healthy volunteers, we found that HLA-DR levels were considerably lower in CD14+CD16+ intermediate (p<0.0001) and CD14lowCD16+ non-classical monocytes populations (p=0.001). Other phenotypic evaluations identified decreases in surface expression of CD86 (p=0.0006), TNFRII (p=0.0001) and increased expression of tissue factor and PD-L1 (p=0.003) on monocytes in melanoma patients. The monocytes had decreased ability to up-regulate CD80 expression and cytokine production following stimulation with toll like 3 receptor agonist. 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 the patient's immune function. These findings open new avenues into examining the role of monocyte populations in melanoma development.
- Received July 16, 2013.
- Revision received November 7, 2013.
- Accepted November 7, 2013.
- Copyright © 2013, American Association for Cancer Research.