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.
journal_name
Cancer Immunol Resjournal_title
Cancer immunology researchauthors
Chavan R,Salvador D,Gustafson MP,Dietz AB,Nevala W,Markovic SNdoi
10.1158/2326-6066.CIR-13-0094subject
Has Abstractpub_date
2014-03-01 00:00:00pages
241-8issue
3eissn
2326-6066issn
2326-6074pii
2326-6066.CIR-13-0094journal_volume
2pub_type
杂志文章abstract::We conducted in vitro studies and a clinical trial for patients with squamous cell carcinoma of the head and neck (SCCHN) to study the relationship between FcγRIIIa polymorphisms and antibody-dependent cellular cytotoxicity (ADCC). In vitro, FcγRIIIa genotype was correlated with ADCC and innate cytotoxicity using natu...
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pub_type: 杂志文章,评审
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pub_type: 杂志文章,评审
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