Generation of potent cytotoxic T lymphocytes against in male patients with non-muscle invasive bladder cancer by dendritic cells loaded with dying T24 bladder cancer cells

Abstract

Background In order to induce a potent cytotoxic T lymphocyte (CTL) response in dendritic cell (DC)-based immunotherapy for bladder cancer, various tumor antigens can be loaded onto DCs.Objective The aim of this study was to establish a method of immunotherapy for male patients with non-muscle invasive bladder cancer (NMIBC), using bladder cancer-specific CTLs generated in vitro by DCs.Materials and Methods Monocyte-derived DCs from bladder cancer patients were induced to mature in a standard cytokine cocktail (IL-1β, TNF-α, IL-6, and PGE2: standard DCs, sDCs) or anα-type 1-polarized DC (αDC1) cocktail (IL-1β, TNF-α, IFN-α, IFN-γ, and polyinosinic:polycytidylic acid) and loaded with the UVB-irradiated bladder cancer cell line, T24. Antigen-loaded αDC1s were evaluated by morphological and functional assays, and the bladder cancer-specific CTL response was analyzed by cytotoxic assay.Results The αDC1s significantly increased the expression of several molecules pertaining to DC maturation, regardless of whether or not the αDC1s were loaded with tumor antigens, relative to sDCs. The αDC1s demonstrated increased production of interleukin-12 both during maturation and after subsequent stimulation with CD40L that was not significantly affected by loading with tumor antigens as compared to that of sDCs. Bladder cancer-specific CTLs targeting autologous bladder cancer cells were successfully induced by αDC1s loaded with dying T24 cells.Conclusion Autologous αDC1s loaded with an allogeneic bladder cancer cell line resulted in increased bladder cancer-specific CTL responses as compared to that with sDCs, and therefore, may provide a novel source of DC-based vaccines that canbe used in immunotherapy for male patients with NMIBC.

Actein induces autophagy and apoptosis in human bladder cancer by potentiating ROS/JNK and inhibiting AKT pathways

“…Bladder cancer is a highly prevalent tumor and is related to substantial morbidity, mortality and cost [ 1 , 2 , 49 ]. The environmental or occupational exposures to carcinogens, particularly tobacco, are the major risk factors for promoting the bladder cancer [ 50 , 51 ]. Currently, despite huge advances have been made, the therapeutic strategies for human bladder cancer are still limited.…”

Phenotypic and functional profile of IFN-α-differentiated dendritic cells (IFN-DCs) from HIV-infected individuals

“…Alternatively, type I IFN has been shown to be a potent stimulus to differentiate or activate MoDCs, as demonstrated in both in vitro and clinical protocols for cancer treatment. [19][20][21][22][23][24][25] In the HIV context, few studies have evaluated the potential of MoDCs differentiated with IFNs inducing an anti-HIV immune response. [26][27][28] Thus, in this study, we focused our attention on evaluating the phenotypic and functional profiles of monocyte-derived IFN-DCs from HIV-infected individuals compared to IL-4-differentiated DCs.…”

Cell Therapies in Bladder Cancer Management

“…Autocrine production of SLC and IL-2 by DCs promoted DC proliferation and cytotoxicity against BC cells that was induced by the co-culture of transfected DCs and T cells. Instead of DC modification, monocyte-derived DCs from NMIBC patients could be induced to mature DCs using a specific cytokine cocktail (IL-1β, tumor necrosis factor (TNF)-α, interferon (IFN)-α, IFN-γ, and polyinosinic:polycytidylic acid) resulting in α-type 1-polarized DCs (αDC1s) [ 28 ]. Autologous αDC1 loaded with the ultraviolet B (UVB)-irradiated human BC cell line T24 increased bladder cancer-specific CTL responses.…”