Dysfunction of Murine Dendritic Cells Induced by Incubation with Tumor Cells

Abstract

In vivo studies showed that dendritic cell (DC) dysfunction occurred in tumor microenvironment. As tumors were composed of many kinds of cells, the direct effects of tumor cells on immature DCs (imDCs) are needed for further studies in vitro. In the present study, bone marrow-derived imDCs were incubated with lymphoma, hepatoma and menaloma cells in vitro and surface molecules in imDCs were determined by flow cytometry. Then, imDCs incubated with tumor cells or control imDCs were further pulsed with tumor lysates and then incubated with splenocytes to perform mixed lymphocyte reaction. The DC-dependent tumor antigen-specific T cell proliferation, and IL-12 secretion were determined by flow cytometry, and enzyme-linked immunosorbent assay respectively.

TGF-β of lung cancer microenvironment upregulates B7H1 and GITRL expression in dendritic cells and is associated with regulatory T cell generation

“…Although literature show a potential role for Tregs in the control of autoimmune or inflammatory diseases (32), the nature of APCs involved in Treg expansion remains poorly understood. Our previous report documented that the tumor cell-DC co-incubation decreased CD80, and CD86 expressions of DCs (9). DCs, especially deficient in CD80 and CD86, appeared to be more efficient than other APCs in inducing TGF-β expansion (33,34).…”

“…In addition to tumor cells, tumor microenvironment is comprised of immune cells, fibroblasts, stromal cells and extracellular matrix (1). Previous studies showed that co-incubation of DCs with different tumor cells could down-regulate the abilities of DCs mediating tumor antigenic-specific CTL priming (9) or inducing human Treg expansion (6). Suppressed DCs functions have been reported in various tumor microenvironment models, in tumor-bearing animals, as well as in cancer patients (24)(25)(26).…”

“…However, this response does not usually occur in most types of human cancer or in animal models, indicating that the dysfunction or immuno-suppression of host immune system might be the main mechanisms by which tumors escape from host immune control (6)(7)(8). Previously, we co-incubated DCs with different tumor cells and found that co-incubation of tumor cell-DCs down-regulated the abilities of DCs in T cell proliferation, IL-12 secretion and tumor antigenic-specific CTL priming (9). Also, Yuan et al established an in vitro incubation system including gastric cancer cell line, with sorting CD4 + T cells and found that gastric cancer cells induced human CD4 + Foxp3 + regulatory T cells (Tregs) through the production of transforming growth factor β1 (TGF-β1) (10).…”

Ataxia-telangiectasia mutated activation mediates tumor necrosis factor-alpha induced MMP-13 up-regulation and metastasis in lung cancer cells

“…Bone marrow-derived immature dendritic cells (imDCs) were prepared as previously described [ 39 ]. Briefly, bone marrow mononuclear cells were prepared from bone marrow suspensions of C57BL/6 mice by depletion of red cells and then were cultured at a density of 1×10 6 cells/ml in RPMI 1640 complete medium with 10 ng/ml of GM-CSF and 1 ng/ml of IL-4.…”

The functional role of L-fucose on dendritic cell function and polarization

“…Broadly, myeloid cells (MCs) play key roles in mediating tumor suppression through early detection of tumor antigens, initializing recruitment of adaptive immune cells to the tumor microenvironment (TME) and elimination of pre-malignant and early-stage tumor cells (5,6). As such, tumor-induced deregulation of the myeloid compartment can significantly influence tumor progression by stimulating tumorigenesis and enforcing an immunosuppressive microenvironment that undermines the efficacy of immunotherapies (7)(8)(9)(10). Pro-tumorigenic MCs, such as myeloid-derived suppressor cells (MDSCs), regulatory dendritic cells (DC reg ), tumor-associated macrophages and neutrophils (TAMs and TANs, respectively), represent an unique challenge for cancer immunotherapies.…”