Increased circulating monocyte MDSCs positively correlate with serum Interleukin-10 in metastatic melanoma patients

• Published in: Innate immunity (London, England) England), 2023-04, Vol.29 (3-4), p.37-44
• Main Authors: Mirjačić Martinović, Katarina, Vuletić, Ana, Tišma Miletić, Nevena, Nedeljković, Milica, Babović, Nada, Matković, Suzana, Jurišić, Vladimir
• Format: Article
• Language: English
• Subjects: CD14 antigen; CD25 antigen; CD4 antigen; Cytokines; Enzyme-linked immunosorbent assay; Flow cytometry; Foxp3 protein; Histocompatibility antigen HLA; HLA-DR Antigens - metabolism; Humans; Immunoregulation; Interleukin 10; Interleukin 8; Interleukin-10 - metabolism; Interleukin-6 - metabolism; L-Lactate dehydrogenase; Leukocytes, Mononuclear; Localization; Lymphocytes B; Lymphocytes T; Melanoma; Melanoma - metabolism; Metastases; Metastasis; Microenvironments; Monocytes; Myeloid-Derived Suppressor Cells; Original; Peripheral blood mononuclear cells; Serum levels; Statistical analysis; Suppressor cells; Transforming growth factor-b; Tumor Microenvironment; γ-Interferon
• ISSN: 1753-4259; 1753-4267
• DOI: 10.1177/17534259231172079

Numerous immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs) and inhibitory cytokines identified in melanoma microenvironment have the important role in immune escape. Therefore, in this study we analyzed monocytic (m)MDSCs in peripheral blood of metastatic melanoma (MM) patients. In peripheral blood of 35 MM patients and 30 healthy controls we analyzed percentage of CD14 + HLA-DR- mMDSCs in monocyte gate and the mean fluorescence intensity of Foxp3 in CD25 + CD4 + regulatory T cells by Flow cytometry. Serum levels of transforming growth factor beta, interferon-gamma, interleukin (IL)-6, IL-8, IL-10 are measured by ELISA assays. In this study MM patients have significantly higher percentage of CD14 + HLA-DR- mMDSCs, as well as increased the baseline mMDSC/PBMC subset (NK, T, B cells, monocytes) ratio. Although there is no significant difference in the percentage of mMDSCs between groups of MM patients with different localization of distant metastasis, patients with elevated serum lactate dehydrogenase (LDH) have statistically significant higher percentage of these cells compared to LDH negative patients. Furthermore, in MM patients there is statistically significant positive correlation between values of IL-10 and the percentage of mMDSCs, only. Therefore, therapeutics that target circulating mMDSCs and IL-10 may have a big importance in the improvement of antitumor immunity in MM patients.