Immunosuppressive activity of CD14⁺ HLA‐DR⁻ cells in squamous cell carcinoma of the head and neck

Abstract

Myeloid‐derived suppressor cells (MDSC) represent a heterogeneous population and have the potential to suppress immune responses via diverse mechanisms. In recent studies, a new subset of MDSC was identified by the markers CD14+ and HLA‐DR− in the peripheral blood from cancer patients. In this study, we investigated the proportions and characteristics of CD14+ HLA‐DR− cells in patients with squamous cell carcinoma of the head and neck (SCCHN). As expected, the percentage of CD14+ HLA‐DR− cells was significantly elevated in patients relative to healthy donors and the sorted CD14+ HLA‐DR− cells were able to suppress effectively both the proliferation and IFN‐γ production of anti‐CD3/anti‐CD28 stimulated T cells, suggesting that CD14+ HLA‐DR− cells in patients with SCCHN contribute to the immune suppressive status. Furthermore, CD14+ HLA‐DR− cells revealed a higher level of CD86 and PD‐L1 expression and transforming growth factor (TGF)‐β production than CD14+ HLA‐DR+ cells. Addition of anti‐CD86 mAb, anti‐PD‐L1 mAb and anti‐TGF‐β mAb partially restored T‐cell proliferation and IFN‐γ production, respectively, indicating that the suppressive effects of CD14+ HLA‐DR− cells appear to be mediated by various molecules, including coinhibitory molecules and cytokines. Our data suggest that CD14+ HLA‐DR− cells act as potent immunosuppressive cells and particularly contribute to tumor escape from the host immune system in patients with SCCHN. (Cancer Sci 2012; 103: 976–983)

CXCL10 and CCL2 mRNA expression in monocytes is inversely correlated with the HLA-DR lower fraction of monocytes in patients with renal cell carcinoma

“…Therefore, it may be of interest to investigate whether the serum concentration of CXCL10 or CCL2 is a useful prognostic marker for patients with cancer. A higher frequency of CD14 + HLA-DR low / -monocytes in RCC patients was observed compared with healthy donors, confirming observations made in previous studies (8)(9)(10) , cells with a lower HLA-DR expression or are negative for HLA-DR; COX2, cyclooxygenase 2; TGF-β, transforming growth factor β; IL, interleukin; CCL2, chemokine (C-C motif) ligand 2; CXCL10, chemokine (C-X-C motif) ligand 10; OSM, oncostatin M; VEGF, vascular endothelial growth factor; RCC, renal cell carcinoma.…”

“…Several studies have revealed that cancer patients exhibit an increase in the number of cluster of differentiation (CD)14 + human leukocyte antigen (HLA)-DR low / -cells, those with a lower HLA-DR expression or are negative for HLA-DR, circulating in the blood (8)(9)(10). CD14 + HLA-DR low / -cells that were isolated from cancer patients were identified to suppress T-cell activation in culture, and thus these CD14 + HLA-DR low / -monocyte populations were considered to act as MDSCs (6,(8)(9)(10).…”

Myeloid-Derived Suppressor Cells Regulate Immune Response in Patients with Chronic Hepatitis B Virus Infection through PD-1–Induced IL-10

“…MDSCs are a heterogeneous population of cells composed of precursors of macrophages, granulocytes, dendritic cells, and myeloid cells at earlier stages of differentiation (5). These cells have been demonstrated to have the potential to suppress immune responses of T cells by way of TGFb, Arg1, programmed death ligand (PD-L) 1, and reactive oxygen species (ROS), as well as by regulatory T cell induction (6)(7)(8)(9)(10)(11). In mice, MDSCs are characterized by the coexpression of Gr-1 and CD11b.…”

PD-1/PD-L1 biology and immunotherapy in HPV-positive oral cancers

“…Treatment with PD-1 dramatically increases the T-cell population and IFN-γ production in head and neck cancer patients, in whom PD-1 positive myeloid-derived suppressor cells were detected in peripheral blood [16].…”

“…However, virus-like particle (the major HPV virion protein L1)-based two prophylactic vaccines: quadrivalent Gardasil (HPV16/18/6/11) and bivalent Cervix (HPV16/18) are available. In 2014, the US FDA has approved a nonavalent vaccine against nine HPV types ( HPV6,11,16,18, 31, 33, 45, 52 and 58) but these vaccines are not commercialized well in developing countries [4][5][6]. …”