Polyriboinosinic Polyribocytidylic Acid (Poly(I:C)) Induces Stable Maturation of Functionally Active Human Dendritic Cells

Verdijk, Rob; Mutis, Tuna; Esendam, Ben; Kamp, J. W.; Melief, C. J. M.; Brand, Anneke; Goulmy, Els

doi:10.4049/jimmunol.163.1.57

Cited by 239 publications

(5 citation statements)

References 28 publications

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“…Unfortunately, no gold standard for effective DC maturation exists. Therefore, we used LPS gram-negative bacterial endotoxins (potent inflammatory mediators) [ 25 ], polyinosinic-polycytidylic acid (a synthetic double-stranded RNA analog that induces stable maturation of functionally active DCs) [ 26 ], and a cocktail maneuver including various cytokines [ 27 ]. Ultimately, we confirmed that the maturated DCs effectively activated T cells specific to certain antigens through IFN-γ secretion.…”

Section: Discussionmentioning

confidence: 99%

Prostate cancer therapy using immune checkpoint molecules to target recombinant dendritic cells

Choi,

Kim,

Lim

et al. 2024

Investig Clin Urol

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Purpose We developed immune checkpoint molecules to target recombinant dendritic cells (DCs) and verified their anti-tumor efficacy and immune response against prostate cancer. Materials and Methods DCs were generated from mononuclear cells in the tibia and femur bone marrow of mice. We knocked down the programmed death ligand 1 (PD-L1) on monocyte-derived DCs through siRNA PD-L1. Cell surface antigens were immune fluorescently stained through flow cytometry to analyze cultured cell phenotypes. Furthermore, we evaluated the efficacy of monocyte-derived DCs and recombinant DCs in a prostate cancer mouse model with subcutaneous TRAMP-C1 cells. Lastly, DC-induced mixed lymphocyte and lymphocyte-only proliferations were compared to determine cultured DCs’ function. Results Compared to the control group, siRNA PD-L1 therapeutic DC-treated mice exhibited significantly inhibited tumor volume and increased tumor cell apoptosis. Remarkably, this treatment substantially augmented interferon-gamma and interleukin-2 production by stimulating T-cells in an allogeneic mixed lymphocyte reaction. Moreover, we demonstrated that PD-L1 gene silencing improved cell proliferation and cytokine production. Conclusions We developed monocyte-derived DCs transfected with PD-L1 siRNA from mouse bone marrow. Our study highlights that PD-L1 inhibition in DCs increases antigen-specific immune responses, corroborating previous immunotherapy methodology findings regarding castration-resistant prostate cancer.

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Section: Discussionmentioning

confidence: 99%

Prostate cancer therapy using immune checkpoint molecules to target recombinant dendritic cells

Choi,

Kim,

Lim

et al. 2024

Investig Clin Urol

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“…We observed that cDC2s upregulated RUNX3 along with CD207 and interferon response genes ISG15 , IFI30 , and IFITM3 in TC. We hypothesize that, in the TME, cDC2s are subjected to IFN-I dependent maturation, potentially via TLR stimulation as it occurs upon viral or poly I:C stimulation ( 71 , 72 ). Consistent with our observation at RNA level, CD207 + CD1a - cDC2s featured a more mature profile at protein level as compared to their CD207 - counterparts.…”

Section: Discussionmentioning

confidence: 99%

Single-cell analysis of myeloid cells in HPV+ tonsillar cancer

Jimenez

Altunbulakli²,

Swoboda³

et al. 2023

Front. Immunol.

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The incidence of human papillomavirus-positive (HPV+) tonsillar cancer has been sharply rising during the last decades. Myeloid cells represent an appropriate therapeutic target due to their proximity to virus-infected tumor cells, and their ability to orchestrate antigen-specific immunity, within the tonsil. However, the interrelationship of steady-state and inflammatory myeloid cell subsets, and their impact on patient survival remains unexplored. Here, we used single-cell RNA-sequencing to map the myeloid compartment in HPV+ tonsillar cancer. We observed an expansion of the myeloid compartment in HPV+ tonsillar cancer, accompanied by interferon-induced cellular responses both in dendritic cells (DCs) and monocyte-macrophages. Our analysis unveiled the existence of four DC lineages, two macrophage polarization processes, and their sequential maturation profiles. Within the DC lineages, we described a balance shift in the frequency of progenitor and mature cDC favoring the cDC1 lineage in detriment of cDC2s. Furthermore, we observed that all DC lineages apart from DC5s matured into a common activated DC transcriptional program involving upregulation of interferon-inducible genes. In turn, the monocyte-macrophage lineage was subjected to early monocyte polarization events, which give rise to either interferon-activated or CXCL-producing macrophages, the latter enriched in advanced tumor stages. We validated the existence of most of the single-cell RNA-seq clusters using 26-plex flow cytometry, and described a positive impact of cDC1 and interferon-activated DCs and macrophages on patient survival using gene signature scoring. The current study contributes to the understanding of myeloid ontogeny and dynamics in HPV-driven tonsillar cancer, and highlights myeloid biomarkers that can be used to assess patient prognosis.

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“… 187 – 189 In vitro, poly-I:C and poly-ICLC induce maturation of human peripheral blood monocyte-derived DCs, leading to secretion of IFN-β and the pro-inflammatory cytokines IL-6 and IL-12, resulting in cross-presentation of exogenous antigens with CD8 + T cells and triggering a Th1-polarized immune response. 190 , 191 Both preclinical and clinical studies have shown that poly-I:C and poly-ICLC are promising adjuvants that enhance antibody production and CD8 + T cell immune responses. 192 , 193 A test in humans showed that combining poly-ICLC with a DC-targeted vaccine induced an innate immune response similar to that of a live virus vaccine, further emphasizing the effectiveness of poly-I:C/poly-ICLC as vaccine adjuvants.…”

Section: Adjuvant Platforms Under Investigationmentioning

confidence: 99%

Vaccine adjuvants: mechanisms and platforms

Zhao

Cai

Jiang

et al. 2023

Sig Transduct Target Ther

126

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Adjuvants are indispensable components of vaccines. Despite being widely used in vaccines, their action mechanisms are not yet clear. With a greater understanding of the mechanisms by which the innate immune response controls the antigen-specific response, the adjuvants’ action mechanisms are beginning to be elucidated. Adjuvants can be categorized as immunostimulants and delivery systems. Immunostimulants are danger signal molecules that lead to the maturation and activation of antigen-presenting cells (APCs) by targeting Toll-like receptors (TLRs) and other pattern recognition receptors (PRRs) to promote the production of antigen signals and co-stimulatory signals, which in turn enhance the adaptive immune responses. On the other hand, delivery systems are carrier materials that facilitate antigen presentation by prolonging the bioavailability of the loaded antigens, as well as targeting antigens to lymph nodes or APCs. The adjuvants’ action mechanisms are systematically summarized at the beginning of this review. This is followed by an introduction of the mechanisms, properties, and progress of classical vaccine adjuvants. Furthermore, since some of the adjuvants under investigation exhibit greater immune activation potency than classical adjuvants, which could compensate for the deficiencies of classical adjuvants, a summary of the adjuvant platforms under investigation is subsequently presented. Notably, we highlight the different action mechanisms and immunological properties of these adjuvant platforms, which will provide a wide range of options for the rational design of different vaccines. On this basis, this review points out the development prospects of vaccine adjuvants and the problems that should be paid attention to in the future.

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Polyriboinosinic Polyribocytidylic Acid (Poly(I:C)) Induces Stable Maturation of Functionally Active Human Dendritic Cells

Cited by 239 publications

References 28 publications

Prostate cancer therapy using immune checkpoint molecules to target recombinant dendritic cells

Prostate cancer therapy using immune checkpoint molecules to target recombinant dendritic cells

Single-cell analysis of myeloid cells in HPV+ tonsillar cancer

Vaccine adjuvants: mechanisms and platforms

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