scholarly journals 178P Glioblastoma multiforme cells down-regulate TNFα-mediated antitumor killer activity of dendritic cells

2021 ◽  
Vol 32 ◽  
pp. S1460
Author(s):  
T. Tyrinova ◽  
S. Mishinov ◽  
O. Leplina ◽  
M. Tikhonova ◽  
V. Stupak ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Glioblastoma Multiforme ◽  
Killer Activity

scholarly journals Antigen-Specific Inhibition of Effector T Cell Function in Humans after Injection of Immature Dendritic Cells

2001 ◽  
Vol 193 (2) ◽  
pp. 233-238 ◽  
Author(s):  
Madhav V. Dhodapkar ◽  
Ralph M. Steinman ◽  
Joseph Krasovsky ◽  
Christian Munz ◽  
Nina Bhardwaj
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Cell Function ◽  
Cd8 T Cell ◽  
Specific Inhibition ◽  
Killer Activity ◽  
Effector T Cell ◽  
T Cell Function ◽  
Cell Immunity

Immunostimulatory properties of dendritic cells (DCs) are linked to their maturation state. Injection of mature DCs rapidly enhances antigen-specific CD4+ and CD8+ T cell immunity in humans. Here we describe the immune response to a single injection of immature DCs pulsed with influenza matrix peptide (MP) and keyhole limpet hemocyanin (KLH) in two healthy subjects. In contrast to prior findings using mature DCs, injection of immature DCs in both subjects led to the specific inhibition of MP-specific CD8+ T cell effector function in freshly isolated T cells and the appearance of MP-specific interleukin 10–producing cells. When pre- and postimmunization T cells were boosted in culture, there were greater numbers of MP-specific major histocompatibility complex tetramer-binding cells after immunization, but these had reduced interferon γ production and lacked killer activity. These data demonstrate the feasibility of antigen-specific inhibition of effector T cell function in vivo in humans and urge caution with the use of immature DCs when trying to enhance tumor or microbial immunity.

Dendritic cell therapy in glioblastoma multiforme

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 3065-3065
Author(s):  
J. Nesselhut ◽  
T. Nesselhut ◽  
R. Chang ◽  
D. Marx ◽  
W. Brockmann ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
Glioblastoma Multiforme ◽  
Combination Therapy ◽  
Clinical Response ◽  
Disease Virus ◽  
Median Survival ◽  
Primary Diagnosis ◽  
Autologous Serum ◽  
Who Grade

3065 Background: Malignant brain tumors belong to the tumors with unfavorable prognosis. The most aggressive form, glioblastoma multiforme (GBM WHO grade IV glioma), is categorized as incurable with median survivals less than 12–18 months and 90–95% of patients surviving less than 2 years. Here we show that immunotherapy with monocyte-derived dendritic cells (MoDC) can induce a clinical response in advanced GMB, especially when combined with the non human pathogenic oncolytic virus NDV (New Castle Disease Virus). Methods: After isolating monocytes from peripheral blood of n=21 patients dendritic cells were generated ex vivo in the presence of recombinant cytokines (IL-4, GM-CSF) and 2,5% autologous serum. If tumor tissue was available the MoDC were primed on day 5 with tumor- lysate and co-cultured with poly:IC and IFN-alpha. The MoDC were harvested on day 7 of culture and administered to the patients, intradermally. In 5 patients NDV was added to the MoDC for one hour prior to administration. These patients received an infusion with NDV one day before vaccination. Results: We were able to induce a clinical response in 33% (n=7) of the treated patients. The median survival after onset of DC-therapy was 10 months. With respect to primary diagnosis the median survival was 19 months with 1- and 2-years survival rates of 81% and 14%, respectively. Improvement of the clinical response can be observed by combination of NDV. None of the 5 patients treated with this combination therapy died of the disease (9–19 months after primary diagnosis). Three of them (60%) show a response with 2 clear partial remissions (40%). Conclusions: Taken together, a dendritic-cell based therapy can be successful in the treatment of GBM. Enhancement of the therapeutically outcome can be induced by a combination therapy with New Castle Disease Virus leading to the suggestion that there may be an interaction between the dendritic cells and the NDV. No significant financial relationships to disclose.

scholarly journals IMMU-50. THE IMMUNE LANDSCAPE OF BLOOD DENDRITIC CELLS IN GLIOBLASTOMA MULTIFORME: IMPLICATIONS FOR DC VACCINATION COMBINED WITH CHECKPOINT INHIBITION

2018 ◽  
Vol 20 (suppl_6) ◽  
pp. vi132-vi132
Author(s):  
Benjamin Kong ◽  
Julius Kim ◽  
Phillip Fromm ◽  
Kim Tam Bui ◽  
Anthony Linton ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Glioblastoma Multiforme ◽  
Checkpoint Inhibition

scholarly journals Dendritic Cell-Based Immunotherapy Treatment for Glioblastoma Multiforme

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Liu Yang ◽  
Geng Guo ◽  
Xiao-yuan Niu ◽  
Jing Liu
Keyword(s):  
Dendritic Cells ◽  
Immune System ◽  
Glioblastoma Multiforme ◽  
Conventional Treatment ◽  
Negative Regulators ◽  
Positive Regulators ◽  
Minimal Damage ◽  
Poor Outcomes ◽  
Antigen Presenting ◽  
Treatment Surgery

Glioblastoma multiforme (GBM) is the most malignant glioma and patients diagnosed with this disease had poor outcomes even treated with the combination of conventional treatment (surgery, chemotherapy, and radiation). Dendritic cells (DCs) are the most powerful antigen presenting cells and DC-based vaccination has the potential to target and eliminate GBM cells and enhance the responses of these cells to the existing therapies with minimal damage to the healthy tissues around them. It can enhance recognition of GBM cells by the patients’ immune system and activate vast, potent, and long-lasting immune reactions to eliminate them. Therefore, this therapy can prolong the survival of GBM patients and has wide and bright future in the treatment of GBM. Also, the efficacy of this therapy can be strengthened in several ways at some degree: the manipulation of immune regulatory components or costimulatory molecules on DCs; the appropriate choices of antigens for loading to enhance the effectiveness of the therapy; regulation of positive regulators or negative regulators in GBM microenvironment.

scholarly journals Interferon-α-inducible Dendritic Cells Matured with OK-432 Exhibit TRAIL and Fas Ligand Pathway-mediated Killer Activity

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Terutsugu Koya ◽  
Ryu Yanagisawa ◽  
Yumiko Higuchi ◽  
Kenji Sano ◽  
Shigetaka Shimodaira
Keyword(s):  
Dendritic Cells ◽  
Fas Ligand ◽  
Interferon Α ◽  
Killer Activity

scholarly journals Defective Regulation of Membrane TNFα Expression in Dendritic Cells of Glioblastoma Patients Leads to the Impairment of Cytotoxic Activity against Autologous Tumor Cells

2020 ◽  
Vol 21 (8) ◽  
pp. 2898
Author(s):  
Tamara Tyrinova ◽  
Olga Leplina ◽  
Sergey Mishinov ◽  
Marina Tikhonova ◽  
Evgeniya Dolgova ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Cytotoxic Activity ◽  
Tumor Cells ◽  
Tumor Cell Line ◽  
Autologous Tumor ◽  
Glioblastoma Cells ◽  
Tumoricidal Activity ◽  
Killer Activity ◽  
Double Stranded Dna ◽  
Antigen Presenting

Besides an antigen-presenting function and ability to induce antitumor immune responses, dendritic cells (DCs) possess a direct tumoricidal activity. We previously reported that monocyte-derived IFNα-induced DCs (IFN-DCs) of glioblastoma multiforme patients express low levels of membrane TNFα molecule (mTNFα) and have impaired TNFα/TNF-R1-mediated cytotoxicity against immortalized tumor cell line HEp-2. However, whether the observed defect could affect killer activity of glioma patient DCs against autologous tumor cells remained unclear. Here, we show that donor IFN-DCs possess cytotoxic activity against glioblastoma cell lines derived from a primary tumor culture. Granule-mediated and TNFα/TNF-R1-dependent pathways were established as the main mechanisms underlying cytotoxic activity of IFN-DCs. Glioblastoma patient IFN-DCs showed lower cytotoxicity against autologous glioblastoma cells sensitive to TNFα/TNFR1-mediated lysis, which was associated with low TNFα mRNA expression and high TACE/ADAM-17 enzyme activity. Recombinant IL-2 (rIL-2) and human double-stranded DNA (dsDNA) increased 1.5-fold cytotoxic activity of patient IFN-DCs against autologous glioblastoma cells. dsDNA, but not rIL-2, enhanced the expression of TNFα mRNA and decreased expression and activity of TACE/ADAM-17 enzyme. In addition, dsDNA and rIL-2 stimulated the expression of perforin and granzyme B (in the presence of dsDNA), suggesting the possibility of enhancing DC cytotoxicity against autologous glioblastoma cells via various mechanisms.

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