Synergistic effect of Toll-like receptor 4 and 7/8 agonists is necessary to generate potent blast-derived dendritic cells in Acute Myeloid Leukemia

Nourizadeh, Maryam; Masoumi, Farimah; Memarian, Ali; Moazzeni, Seyed Mohammad; Hadjati, Jamshid

doi:10.1016/j.leukres.2012.04.007

Cited by 16 publications

(16 citation statements)

References 43 publications

(66 reference statements)

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“…Specific DC surface markers (immunophenotyping) change during the differentiation of DCs from the precursors (monocytes, bone marrow precursors, blasts, etc.). As a results of our and previous studies on AML-DCs, CD14+ and CD86+, blasts are more susceptible to be differentiated to AML-DCs [43,[61][62][63]. Contrary to CD14 which decreases during the differentiation of blast into immature and mature DCs, the expression pattern and especially mean florescent intensity (MFI) of CD86 increase gradually until full maturity of DCs.…”

Section: Possibility Of Generating Blast-derived Dcssupporting

confidence: 49%

“…We found that a combination of LPS + R848 and LPS + R848 + poly(I:C) provide the highest percentages of DCs expressing HLA-DR and CD86. High expression of these two molecules was accompanied with a strong allostimulatory capacity of the relevant AML-DCs in allo-MLR [43]. Similarly, Bohnenkamp et al indicated that potent and efficient T-helper cell type 1 response can be elicited by monocyte-derived DCs after TLR engagement with poly(I:C) or LPS and R848 [58].…”

Section: Possibility Of Generating Blast-derived Dcsmentioning

confidence: 96%

“…CD40, CD86, CD1a, CD83 and CCR7) and revealed the other functional capacities of antigen presenting cells. We also tried to find the most efficient maturation cocktails among different combinations of TLR ligands as recently introduced potent adjuvants [43,44]. Synergistic effect of TLR-agonists on DC maturation Recent studies have focused on attempts to provide appropriate guidelines in order to generate optimally matured DCs with the ability of migration toward lymph nodes and response to licensing stimuli, following administration to a patient with cancer [14].…”

Section: Possibility Of Generating Blast-derived Dcsmentioning

confidence: 99%

“…Kalinski and colleagues have introduced a "megacytokine cocktail" consisting of 5 reagents (TNF-α, IL-1β, Poly (I:C), IFN-α, and IFN-γ), conferring superior immunogenicity and more potent CTL responses [46]. As a result, cocktails containing synthetic TLR agonists such as Poly (I:C) (TLR3 agonist) or R848 (TLR7/8 agonists) came out as attractive alternatives for the induction of DC maturation and subsequent Th1 immune responses via high production of IL-12(p70) [47,48]. The co-stimulatory features of DCs can be launched by triggering of pathogen recognition receptors (PRRs) such as Toll-like receptors (TLRs), which have a critical role in sensing microbial or viral structures called pathogen-associated molecular patterns (PAMPs) [49,50].…”

Section: Possibility Of Generating Blast-derived Dcsmentioning

confidence: 99%

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Effective Dendritic Cell-based Immunotherapeutic Vaccines for Acute Myeloid Leukemia (AML)

Nourizadeh

Hadjati

2014

vacres

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Section: Possibility Of Generating Blast-derived Dcssupporting

confidence: 49%

Section: Possibility Of Generating Blast-derived Dcsmentioning

confidence: 96%

Section: Possibility Of Generating Blast-derived Dcsmentioning

confidence: 99%

Section: Possibility Of Generating Blast-derived Dcsmentioning

confidence: 99%

See 2 more Smart Citations

Effective Dendritic Cell-based Immunotherapeutic Vaccines for Acute Myeloid Leukemia (AML)

Nourizadeh

Hadjati

2014

vacres

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“…Furthermore, Arg(9) would also be well suited for c-di-GMP delivery since it can bypass endosomal barriers, and transfer its cargo into the cytosol [33]. Data presented herein demonstrate that c-di-GMP/Arg(9) complexes are internalized approximately fourfold more efficiently than the free molecule and the overall potency of the CDN is increased.Combined activation of multiple PRRs can result in synergistic effects, triggering robust adaptive immune responses [34][35][36]. Following this concept, we chose to activate the TLR-dependent and TLR-independent DNA recognition pathways through combined use of CpG ODN and CDNs.…”

mentioning

confidence: 99%

Enhanced immunostimulatory activity of cyclic dinucleotides on mouse cells when complexed with a cell‐penetrating peptide or combined with CpG

et al. 2015

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Recognition of pathogen-derived nucleic acids by immune cells is critical for the activation of protective innate immune responses. Bacterial cyclic dinucleotides (CDNs) are small nucleic acids that are directly recognized by the cytosolic DNA sensor STING (stimulator of IFN genes), initiating a response characterized by proinflammatory cytokine and type I IFN production. Strategies to improve the immune stimulatory activities of CDNs can further their potential for clinical development. Here, we demonstrate that a simple complex of cylic-di-GMP with a cell-penetrating peptide enhances both cellular delivery and biological activity of the cyclic-di-GMP in murine splenocytes. Furthermore, our findings establish that activation of the TLR-dependent and TLR-independent DNA recognition pathways through combined use of CpG oligonucleotide (ODN) and CDN results in synergistic activity, augmenting cytokine production (IFN-α/β, IL-6, TNF-α, IP-10), costimulatory molecule upregulation (MHC class II, CD86), and antigen-specific humoral and cellular immunity. Results presented herein indicate that 3 3 -cGAMP, a recently identified bacterial CDN, is a superior stimulator of IFN genes ligand than cyclic-di-GMP in human PBMCs. Collectively, these findings suggest that the immune-stimulatory properties of CDNs can be augmented through peptide complexation or synergistic use with CpG oligonucleotide and may be of interest for the development of CDN-based immunotherapeutic agents. Keywords:Arginine peptide (nona-arginine) r cGAMP r CpG ODN r Cyclic-di-GMP r Immunostimulation See accompanying article by Temizoz et al.Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionDetection of pathogen-derived nucleic acids by innate immune cells is critical for the initiation of protective responses against bacterial, viral, and fungal pathogens. Pathogen-derived nucleic acids are sensed based on their sequence, structure, nucleotide Correspondence: Dr. Mayda Gursel e-mail: mgursel@metu.edu.tr modifications, and their intracellular localization. So far, several nucleic acid sensors have been identified, including the endosomal TLRs TLR3, TLR7/TLR8, and TLR9 that recognize dsRNA, ssRNA, and CpG-containing DNA; cytosolic dsRNA sensors RIG-I, MDA5, LGP2; and a plethora of cytosolic receptors dedicated for dsDNA recognition (DAI, AIM2, RNA polymerase III, IFI16, DEAD-box helicase DDX41) [1]. Signaling in response to cytosolic DNA depends on the expression of the adaptor protein STING (stimulator of IFN genes, also known as TMEM173, MPYS, MITA and ERIS) and proceeds through the TBK1-IRF3 axis, C 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2015. 45: 1170-1179 Innate immunity 1171 culminating in type I IFN production [2, 3]. STING itself is not a DNA-recognition molecule. However, it can directly recognize cyclic dinucleotides (CDNs) such as the bacteria-derived molecule cyclic-di-GMP (c-di-GMP) [4]. Although CDNs were thought to functio...

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Impaired monocyte‐derived dendritic cell phenotype in prostate cancer patients: A phenotypic comparison with healthy donors

Bakhshi,

Nourizadeh,

Sharifi

et al. 2024

Cancer Reports

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BackgroundDendritic cells (DCs) play a crucial role in immunity. Research on monocyte‐derived DCs (Mo‐DCs) cancer vaccines is in progress despite limited success in clinical trials. This study focuses on Mo‐DCs generated from prostate cancer (PCA) patients, comparing them with DCs from healthy donors (HD‐DCs).MethodsMo‐DCs were isolated from PCA patient samples, and their phenotype was compared to HD‐DCs. Key parameters included monocyte count, CD14 expression, and the levels of maturation markers (HLA‐DR, CD80, CD86) were assessed.ResultsPCA samples exhibited a significantly lower monocyte count and reduced CD14 expression compared to healthy samples (p ⟨ 0.0001). Additionally, PCA‐DCs expressed significantly lower levels of maturation markers, including HLA‐DR, CD80, and CD86, when compared to HD‐DCs (p = 0.123, p = 0.884, and p = 0.309, respectively).ConclusionThe limited success of DC vaccines could be attributed to impaired phenotypic characteristics. These observations suggest that suboptimal characteristics of Mo‐DCs generated from cancer patient blood samples might contribute to the limited success of DC vaccines. Consequently, this study underscores the need for alternative strategies to enhance the features of Mo‐DCs for more effective cancer immunotherapies.

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Synergistic effect of Toll-like receptor 4 and 7/8 agonists is necessary to generate potent blast-derived dendritic cells in Acute Myeloid Leukemia

Cited by 16 publications

References 43 publications

Effective Dendritic Cell-based Immunotherapeutic Vaccines for Acute Myeloid Leukemia (AML)

Effective Dendritic Cell-based Immunotherapeutic Vaccines for Acute Myeloid Leukemia (AML)

Enhanced immunostimulatory activity of cyclic dinucleotides on mouse cells when complexed with a cell‐penetrating peptide or combined with CpG

Impaired monocyte‐derived dendritic cell phenotype in prostate cancer patients: A phenotypic comparison with healthy donors

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