Plasmacytoid Dendritic Cells as a Novel Cell-Based Cancer Immunotherapy

Hernández, Sabina Sánchez; Jakobsen, Martin R.; Bak, Rasmus O.

doi:10.3390/ijms231911397

Cited by 17 publications

(13 citation statements)

References 83 publications

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“…43 In addition, our immune infiltration analysis results showed that the expression of CEL was significantly negatively correlated with plasmacytoid dendritic cell, and plasmacytoid dendritic cell were an important link in the initiation of adaptive immune response, participating in the immune inflammatory process of promoting atherosclerosis. 44,45 In our study, CEL expression was downregulated in peripheral blood samples from CAD patients, which means that plasmacytoid dendritic cell will be recruited and activated, and promote the occurrence of atherosclerosis, which also confirms the previous view.…”

supporting

confidence: 90%

Immune Cell Infiltration Analysis Based on Bioinformatics Reveals Novel Biomarkers of Coronary Artery Disease

He,

Muhetaer,

et al. 2023

JIR

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Background: Coronary artery disease (CAD) is a multifactorial immune disease, but research into the specific immune mechanism is still needed. The present study aimed to identify novel immune-related markers of CAD. Methods: Three CAD-related datasets (GSE12288, GSE98583, GSE113079) were downloaded from the Gene Expression Integrated Database. Gene ontology annotation, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis and weighted gene coexpression network analysis were performed on the common significantly differentially expressed genes (DEGs) of these three data sets, and the most relevant module genes for CAD obtained. The immune cell infiltration of module genes was evaluated with the CIBERSORT algorithm, and characteristic genes accompanied by their diagnostic effectiveness were screened by the machine-learning algorithm least absolute shrinkage and selection operator (LASSO) regression analysis. The expression levels of characteristic genes were evaluated in the peripheral blood mononuclear cells of CAD patients and healthy controls for verification. Results: A total of 204 upregulated and 339 downregulated DEGs were identified, which were mainly enriched in the following pathways: "Apoptosis", "Th17 cell differentiation", "Th1 and Th2 cell differentiation", "Glycerolipid metabolism", and "Fat digestion and absorption". Five characteristic genes, LMAN1L, DOK4, CHFR, CEL and CCDC28A, were identified by LASSO analysis, and the results of the immune cell infiltration analysis indicated that the proportion of immune infiltrating cells (activated CD8 T cells and CD56 DIM natural killer cells) in the CAD group was lower than that in the control group. The expressions of CHFR, CEL and CCDC28A in the peripheral blood of the healthy controls and CAD patients were significantly different. Conclusion:We identified CHFR, CEL and CCDC28A as potential biomarkers related to immune infiltration in CAD based on public data sets and clinical samples. This finding will contribute to providing a potential target for early noninvasive diagnosis and immunotherapy of CAD.

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supporting

confidence: 90%

Immune Cell Infiltration Analysis Based on Bioinformatics Reveals Novel Biomarkers of Coronary Artery Disease

He,

Muhetaer,

et al. 2023

JIR

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“…Similarly, cigarette smoke extract-induced NETs also promoted pDCs maturation and activation ( 125 ). The role of pDCs in TME is still ambiguous now ( 126 ). Thus, we hold the opinion that whether NETs-mediated pDCs activation display active immunity functions or involved in immune tolerance is determined by the specific tumor microenvironmental.…”

Section: Nets In Immune Cellsmentioning

confidence: 99%

Neutrophil extracellular traps in tumor progression and immunotherapy

Yan

Sun

et al. 2023

Front. Immunol.

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Tumor immunity is a growing field of research that involves immune cells within the tumor microenvironment. Neutrophil extracellular traps (NETs) are neutrophil-derived extracellular web-like chromatin structures that are composed of histones and granule proteins. Initially discovered as the predominant host defense against pathogens, NETs have attracted increasing attention due to they have also been tightly associated with tumor. Excessive NET formation has been linked to increased tumor growth, metastasis, and drug resistance. Moreover, through direct and/or indirect effects on immune cells, an abnormal increase in NETs benefits immune exclusion and inhibits T-cell mediated antitumor immune responses. In this review, we summarize the recent but rapid progress in understanding the pivotal roles of NETs in tumor and anti-tumor immunity, highlighting the most relevant challenges in the field. We believe that NETs may be a promising therapeutic target for tumor immunotherapy.

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“…This vaccine consists of a cell line, named "PDC*line", originating from the blood of a patient with plasmacytoid dendritic cell (PDC) leukemia that can be loaded with relevant tumor antigen-derived peptides [8,9]. PDCs are a subtype of DCs playing an essential role in the immune response against viruses through type I interferon secretion [10][11][12]. They also have strong antigen presentation capabilities but have rarely been exploited as a cancer vaccine due to their scarcity [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

“…PDCs are a subtype of DCs playing an essential role in the immune response against viruses through type I interferon secretion [10][11][12]. They also have strong antigen presentation capabilities but have rarely been exploited as a cancer vaccine due to their scarcity [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

A New Plasmacytoid Dendritic Cell-Based Vaccine in Combination with Anti-PD-1 Expands the Tumor-Specific CD8+ T Cells of Lung Cancer Patients

Hannani¹,

Leplus²,

Laurin

et al. 2023

IJMS

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The purpose of immune checkpoint inhibitor (ICI)-based therapies is to help the patient’s immune system to combat tumors by restoring the immune response mediated by CD8+ cytotoxic T cells. Despite impressive clinical responses, most patients do not respond to ICIs. Therapeutic vaccines with autologous professional antigen-presenting cells, including dendritic cells, do not show yet significant clinical benefit. To improve these approaches, we have developed a new therapeutic vaccine based on an allogeneic plasmacytoid dendritic cell line (PDC*line), which efficiently activates the CD8+ T-cell response in the context of melanoma. The goal of the study is to demonstrate the potential of this platform to activate circulating tumor-specific CD8+ T cells in patients with lung cancer, specifically non-small-cell lung cancer (NSCLC). PDC*line cells loaded with peptides derived from tumor antigens are used to stimulate the peripheral blood mononuclear cells of NSCLC patients. Very interestingly, we demonstrate an efficient activation of specific T cells for at least two tumor antigens in 69% of patients irrespective of tumor antigen mRNA overexpression and NSCLC subtype. We also show, for the first time, that the antitumor CD8+ T-cell expansion is considerably improved by clinical-grade anti-PD-1 antibodies. Using PDC*line cells as an antigen presentation platform, we show that circulating antitumor CD8+ T cells from lung cancer patients can be activated, and we demonstrate the synergistic effect of anti-PD-1 on this expansion. These results are encouraging for the development of a PDC*line-based vaccine in NSCLC patients, especially in combination with ICIs.

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Plasmacytoid Dendritic Cells as a Novel Cell-Based Cancer Immunotherapy

Cited by 17 publications

References 83 publications

Immune Cell Infiltration Analysis Based on Bioinformatics Reveals Novel Biomarkers of Coronary Artery Disease

Immune Cell Infiltration Analysis Based on Bioinformatics Reveals Novel Biomarkers of Coronary Artery Disease

Neutrophil extracellular traps in tumor progression and immunotherapy

A New Plasmacytoid Dendritic Cell-Based Vaccine in Combination with Anti-PD-1 Expands the Tumor-Specific CD8+ T Cells of Lung Cancer Patients

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