IFNγ Markedly Cooperates with Intratumoral Dendritic Cell Vaccine in Dog Tumor Models

Abstract

Dendritic cell (DC)-based immunotherapy can trigger effective immune responses against cancer in human patients. Although accompanied by little toxicity, further improvements are needed to optimize immune responses for fully satisfactory clinical outcomes. IFNγ, a potent inducer of T helper type 1 immune responses, is considered an important tool to realize improvements. In this study, we sought to clarify the effect of IFNγ on the maturation and activation of DCs and the clinical outcome of DC-based cancer therapy in dogs.

Cucurbitacin E suppresses cytokine expression in human Jurkat T cells through down-regulating the NF-κB signaling

“…Pro-inflammatory cytokine TNF-α can augment inflammatory responses by acting on many immune and non-immune cells as well as by stimulating the secretion of other pro-inflammatory cytokines [24,25]. Besides, IFN-γ can promote both the innate and adaptive immune responses against tumor cells and a variety of infectious agents [26,27]; it is also critical in the development of inflammatory diseases [27]. Therefore, by attenuating the expression of these critical cytokines, CucE may suppress adaptive immune responses mediated by T cells, thereby dampening ongoing inflammatory responses and contributing to its therapeutic activity in controlling inflammatory diseases.…”

Intratumoral immunotherapy for melanoma

“…I.t. injection of immature DCs and IFNgamma into malignant tumors in dogs produced anti-tumor immunity including four complete responses and two partial responses out of seven treated dogs [99]. In B16 melanoma, i.t.…”

Nicotine stimulated bone marrow-derived dendritic cells could augment HBV specific CTL priming by activating PI3K-Akt pathway

“…As ex vivo-generated, antigen-loaded DCs have poor anti-tumor effects [40][41][42], new alternatives such as IFN-␥ DCs or IL-15 DCs are emerging and have better efficiency in inducing antigen-specific CTL priming [27][28][29]. Nicotine, known as a chemical compound with advantages of chemical stability and economic, caught much attention for its stimulation to enhance DCs' ability of mediating T cell proliferation.…”

“…Recently, it has been reported that IFN-␥, IL-15 and IL-18 have bioactivities to augment DCs' functions [27][28][29]. We compared the stimulation efficiency of nicotine with other cytokines, as potential clinical implication of nicotine stimulated DCs was considered.…”

“…As HBV antigen pulsed DCs can efficiently augment HBV-specific CTL response in chronically infected HBV patients and HBV transgenic mice [24][25][26], the roles of nicotine-treated DCs in HBV immunotherapy still need to be determined. IFN-␥, IL-15 and IL-18 have recently been reported to augment DCs' functions [27][28][29]. For this reason, the stimulation efficiencies of nicotine on DCs should be compared with other cytokines such as IFN-␥, when potential clinical implication was considered.…”