Enhanced Protective Immunity Derived from Dendritic Cells with Phagocytosis of CD40 Ligand Transgene-engineered Apoptotic Tumor Cells via Increased Dendritic Cell Maturation

Parameswaran, Sreejit; Khalil, Muhammad; Ahmed, Khawaja Ashfaque; Sharma, Rajendra K.; Xiang, Jim

doi:10.5301/tj.5000297

Cited by 5 publications

(5 citation statements)

References 33 publications

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“…42 We also reported that DCs that phagocytose irradiation-treated tumor cells induce potent antitumor CTL responses and immunity in animal models. 17 In this study, we showed that 65°C-treated tumor cells trigger DC maturation and that DCs that phagocytose 65°C-treated tumor cells stimulate more efficient OVA-specific CTL responses than DCs that phagocytose 45°C-treated tumor cells.…”

Section: Discussionmentioning

confidence: 66%

“…Student's t-test was applied to compare the variables from different groups. 17 A value of p < 0.05 was considered statistically significant.…”

Section: Discussionmentioning

confidence: 99%

“…Live cells were purified with Ficoll-Paque gradient centrifugation, stained with a PE-labeled anti-CD11c antibody (red) for cell surface CD11c molecules and 4′,6-diamidino-2-phenylindole (DAPI; blue) for nuclei and then analyzed by flow cytometry and confocal microscopy according to a protocol we previously described. 17 Alternatively, DCs were fixed with 4% paraformaldehyde for electron microscopy to visualize DC phagocytosis according to a protocol we previously reported. 16 To assess the immunogenicity of the DCs, we prepared DCs that phagocytosed heat-treated tumor cells during the overnight incubation of the DCs with the 45°C-treated and 65°C-treated tumor cells at a ratio of 1:2 in the absence or presence of CpG (10 µg/mL).…”

Section: Methodsmentioning

confidence: 99%

“…12 In conjunction with some other reports, [13][14][15] we previously demonstrated that dendritic cells (DCs) that phagocytose apoptotic EG7 and BL6-10 OVA tumor cells, which were both engineered to express OVA as a model tumor antigen, induced potent OVAspecific CTL responses detected by flow cytometry. 16,17 In addition, we have recently constructed and validated a custommade RFA device capable of generating RFA-induced cell death in hepatoma tissue. 18,19 With minor modifications, this device is suitable for studying RFA-induced CTL responses in tumor models in vivo.…”

Section: Introductionmentioning

confidence: 99%

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TLR9 agonist enhances radiofrequency ablation-induced CTL responses, leading to the potent inhibition of primary tumor growth and lung metastasis

Zhang

Yuan

et al. 2018

Cell Mol Immunol

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Radiofrequency ablation (RFA) is the most common approach to thermal ablation for cancer therapy. Unfortunately, its efficacy is limited by incomplete ablation, and further optimization of RFA is required. Here, we demonstrate that incubation at 65°C triggers more EG7 tumor cell death by necrosis than treatment at 45°C, and the 65°C-treated cells are more effective at inducing antigenspecific CD8 + cytotoxic T lymphocyte (CTL) responses after injection in mice than the 45°C-treated ones. Dendritic cells (DCs) that phagocytose 65°C-treated EG7 cells become mature with upregulated MHCII and CD80 expression and are capable of efficiently inducing effector CTLs in mouse tumor models. RFA (65°C) therapy of EG7 tumors induces large areas of tumor necrosis and stimulates CTL responses. This leads to complete regression of small (~100 mm 3) tumors but fails to suppress the growth of larger (~350 mm 3) tumors. The administration of the Toll-like receptor-9 (TLR9) agonist unmethylated cytosine-phosphorothioate-guanine oligonucleotide (CpG) to DCs phagocytosing 65°C-treated EG7 cells enhances the expression of MHCII and CD40 on DCs as well as DC-induced stimulation of CTL responses. Importantly, the intratumoral administration of CpG following RFA also increases the frequencies of tumor-associated immunogenic CD11b − CD11c + CD103 + DC2 and CD11b + F4/80 + MHCII + M1 macrophages and increases CD4 + and CD8 + T-cell tumor infiltration, leading to enhanced CD4 + T cell-dependent CTL responses and potent inhibition of primary RFA-treated or distant untreated tumor growth as well as tumor lung metastasis in mice bearing larger tumors. Overall, our data indicate that CpG administration, which enhances RFA-induced CTL responses and ultimately potentiates the inhibition of primary tumor growth and lung metastasis, is a promising strategy for improving RFA treatment, which may assist in optimizing this important cancer therapy.

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Section: Discussionmentioning

confidence: 66%

“…Student's t-test was applied to compare the variables from different groups. 17 A value of p < 0.05 was considered statistically significant.…”

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

TLR9 agonist enhances radiofrequency ablation-induced CTL responses, leading to the potent inhibition of primary tumor growth and lung metastasis

Zhang

Yuan

et al. 2018

Cell Mol Immunol

Self Cite

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“…This responses can switch to a pro-inflammatory status when the phagocytic cells become DCs. It has been widely reported in the establishment of apoptotic tumour cell-phagocytosed DCs for immunotherapy [ 96 – 100 ]. DCs that acquired antigens from apoptotic tumour cells are able to induce major histocompatibility complex (MHC) class I-restricted cytotoxic T cells and anti-tumor immunity [ 98 ].…”

Section: Comparison Of Immunotherapymentioning

confidence: 99%

Comparison of immunotherapy mediated by apoptotic bodies, microvesicles and exosomes: apoptotic bodies’ unique anti-inflammatory potential

Wen,

Creaven,

Luan

et al. 2023

J Transl Med

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Immunotherapy, including immunostimulation and immunosuppression, has seen significant development in the last 10 years. Immunostimulation has been verified as effective in anti-cancer treatment, while immunosuppression is used in the treatment of autoimmune disease and inflammation. Currently, with the update of newly-invented simplified isolation methods and the findings of potent triggered immune responses, extracellular vesicle-based immunotherapy is very eye-catching. However, the research on three main types of extracellular vesicles, exosomes, microvesicles and apoptotic bodies, needs to be more balanced. These three subtypes share a certain level of similarity, and at the same time, they have their own properties caused by the different methods of biogensis. Herein, we summarized respectively the status of immunotherapy based on each kind of vesicle and discuss the possible involved mechanisms. In conclusion, we highlighted that the effect of the apoptotic body is clear and strong. Apoptotic bodies have an excellent potential in immunosuppressive and anti-inflammatory therapies .

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Quantification and functional evaluation of CD40L production from the adenovirus vector ONCOS-401

2018

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Adaptive immunity involves activation of T cells via antigen presentation by antigen presenting cells (APCs) along with the action of co-stimulatory molecules and pattern recognition receptors. Cluster of differentiation 40 (CD40) is one such costimulatory molecule that is expressed on APCs that binds to CD40 ligand (CD40L) on T helper cells and activates a signaling cascade, subsequently resulting in a wide range of immune and inflammatory responses. Considering its important role in regulation of immune response, CD40/40 L has been used for developing antitumor vaccines. In this study, we developed methods for evaluating and quantifying the activity of CD40L expressed from an adenovirus vector ONCOS-401. Our results show that the ONCOS-401 vector produces functional CD40L, which can bind and activate a NF-κB-dependent signaling cascade, leading to secreted embryonic alkaline phosphatase reporter production in HEK293-BLUE cells. In addition, quantification of CD40L production using enzyme-linked immunosorbent assay and HEK-293 BLUE reporter cells showed reproducibly higher recovery of CD40L from ONCOS-401 than from the negative control vector or uninfected cells with consistent inter and intra-assay precision. Thus, a rapid and easy method for quantifying and assessing CD40L production and activity from adenovirus vectors would support the assessment of efficacy of the vector for gene therapy - this was the objective of our study.

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Enhanced Protective Immunity Derived from Dendritic Cells with Phagocytosis of CD40 Ligand Transgene-engineered Apoptotic Tumor Cells via Increased Dendritic Cell Maturation

Abstract: Dendritic cells that have phagocytized CD40L-expressing apoptotic tumor cells appear to offer new strategies in DC cancer vaccines.

Cited by 5 publications

References 33 publications

TLR9 agonist enhances radiofrequency ablation-induced CTL responses, leading to the potent inhibition of primary tumor growth and lung metastasis

TLR9 agonist enhances radiofrequency ablation-induced CTL responses, leading to the potent inhibition of primary tumor growth and lung metastasis

Comparison of immunotherapy mediated by apoptotic bodies, microvesicles and exosomes: apoptotic bodies’ unique anti-inflammatory potential

Quantification and functional evaluation of CD40L production from the adenovirus vector ONCOS-401

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