Natural Killer–Dendritic Cell Interactions in Liver Cancer: Implications for Immunotherapy

Cazzetta, Valentina; Franzese, Sara; Carenza, Claudia; Bella, Silvia Della; Mikulak, Joanna; Mavilio, Domenico

doi:10.3390/cancers13092184

Cited by 23 publications

(14 citation statements)

References 214 publications

(271 reference statements)

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“…NK cells also interact with DCs, through cell-to-cell contact and soluble mechanisms, recently reviewed elsewhere ( 13 ). As for NK cell-monocyte crosstalk, also in the case of NK cells and DCs exists a bidirectional interaction, responsible on one hand for reciprocal cell activation, on the other hand for homeostatic control aimed at preventing excessive immune activation.…”

Section: Nk Cell Crosstalk With Other Immune Cells In Sars-cov-2 Infe...mentioning

confidence: 99%

“…NKp46 and NKp30 are expressed on virtually all resting NK cells, whereas NKp44 expression is acquired upon NK cell activation. These molecules are important for inducing NK cell cytotoxic function against target stressed-cells and in the crosstalk with other cell types, such as dendritic cells (DCs) ( 13 ). Other important activating NK receptors are the C-type lectin-like receptors NKG2D and NKG2C and the activating Killer Immunoglobulin-Like Receptors (KIRs).…”

Section: Introductionmentioning

confidence: 99%

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Natural Killer Cells in SARS-CoV-2 Infection: Pathophysiology and Therapeutic Implications

et al. 2022

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Natural Killer (NK) cells are lymphocytes of the innate immunity that play a crucial role in the control of viral infections in the absence of a prior antigen sensitization. Indeed, they display rapid effector functions against target cells with the capability of direct cell killing and antibody-dependent cell-mediated cytotoxicity. Furthermore, NK cells are endowed with immune-modulatory functions innate and adaptive immune responses via the secretion of chemokines/cytokines and by undertaking synergic crosstalks with other innate immune cells, including monocyte/macrophages, dendritic cells and neutrophils. Recently, the Coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread globally. Although the specific role of NK cells in COVID-19 pathophysiology still need to be explored, mounting evidence indicates that NK cell tissue distribution and effector functions could be affected by SARS-CoV-2 infection and that a prompt NK cell response could determine a good clinical outcome in COVID-19 patients. In this review, we give a comprehensive overview of how SARS-CoV-2 infection interferes with NK cell antiviral effectiveness and their crosstalk with other innate immune cells. We also provide a detailed characterization of the specific NK cell subsets in relation to COVID-19 patient severity generated from publicly available single cell RNA sequencing datasets. Finally, we summarize the possible NK cell-based therapeutic approaches against SARS-CoV-2 infection and the ongoing clinical trials updated at the time of submission of this review. We will also discuss how a deep understanding of NK cell responses could open new possibilities for the treatment and prevention of SARS-CoV-2 infection.

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Section: Nk Cell Crosstalk With Other Immune Cells In Sars-cov-2 Infe...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Natural Killer Cells in SARS-CoV-2 Infection: Pathophysiology and Therapeutic Implications

et al. 2022

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“…In our study, we found that PDSS1 in HCC was negatively related to dendritic cells (DCs, pDCs), cytotoxic cells, and CD8 T cells. DCs are a type of antigen-presenting cell which have an important regulatory effect on tumor immune response, and can positively regulate the immune response to HCC ( 31 , 32 ). In addition, CD8 + T cells can secrete cytotoxic particles, making them a type of cytotoxic cell that plays an important role in antitumor immunity ( 33 , 34 ).…”

Section: Discussionmentioning

confidence: 99%

A novel HCC prognosis predictor PDSS1 affects the cell cycle through the STAT3 signaling pathway in HCC

Rao

Yao

et al. 2022

Front. Oncol.

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Decaprenyl diphosphate synthase subunit 1 (PDSS1) is closely related to a variety of human diseases, but its expression pattern and biological function in HCC have not been studied to date.MethodsThe expression level of PDSS1 was analyzed using the TCGA and GEO databases. The relationships between PDSS1 and patient clinicopathological characteristics were verified based on TCGA clinical data. Additionally, the co-expressed genes of PDSS1were investigated and Gene Set Enrichment Analysis (GSEA) was conducted using LinkedOmics. Next, the association between PDSS1 and immune infiltration was determined using version 1.34.0 of the GSVA package. EdU assay, colony-formation assay, transwell assay, wound-healing assay, and flow cytometry analysis were used to assess the effect of PDSS1 on the cell phenotype.ResultsPDSS1 was upregulated in HCC compared with adjacent tissues. High PDSS1 in HCC was associated with poor overall survival, disease-specific survival, and progress-free interval. Results suggested that PDSS1 may activate multiple oncogenic pathways in HCC, especially those involved in the cell cycle. The expression of PDSS1 was significantly related to Th2 cells, TFH, T helper cells, NK CD56bright cells, cytotoxic cells, DC, CD8 T cells, and neutrophils. PDSS1 knockdown inhibited cell proliferation, cell cycle, migration and invasion. Furthermore, PDSS1 acted as an oncogene through the STAT3 signaling pathway.ConclusionOur study reveals that a high level of PDSS1 is significantly correlated with poor patient prognosis and immune cell infiltration in HCC. PDSS1 may be a novel biomarker and potential therapeutic target for HCC.

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“…Thus, tumor-cell material is released that can be processed by further DCs and be presented to T cells [39]. As activation of NK cells is mediated by IL-12 and type I interferons [40], BDCs activated with R848 + poly(I:C) demonstrated potent NK-cell activation with respect to CD69 expression and IFN-γ secretion. Importantly, NK-cell activation has been shown to correlate with clinical outcomes in several clinical trials, including those of a DC vaccine targeting WT1 in AML [39,41,42].…”

Section: Discussionmentioning

confidence: 99%

Blood DCs activated with R848 and poly(I:C) induce antigen-specific immune responses against viral and tumor-associated antigens

Hänel

Angerer

Petry

et al. 2021

Cancer Immunol Immunother

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Monocyte-derived Dendritic cells (DCs) have successfully been employed to induce immune responses against tumor-associated antigens in patients with various cancer entities. However, objective clinical responses have only been achieved in a minority of patients. Additionally, generation of GMP-compliant DCs requires time- and labor-intensive cell differentiation. In contrast, Blood DCs (BDCs) require only minimal ex vivo handling, as differentiation occurs in vivo resulting in potentially better functional capacities and survival. We aimed to identify a protocol for optimal in vitro activation of BDCs including the three subsets pDCs, cDC1s, and cDC2s. We evaluated several TLR ligand combinations and demonstrated that polyinosinic:polycytidylic acid [poly(I:C)] and R848, ligands for TLR3 and TLR7/8, respectively, constituted the optimal combination for inducing a positive co-stimulatory profile in all BDC subsets. In addition, TLR3 and TLR7/8 activation led to high secretion of IFN-α and IL-12p70. Simultaneous as opposed to separate tailored activation of pDCs and cDCs increased immunostimulatory capacities, suggesting that BDC subsets engage in synergistic cross-talk during activation. Stimulation of BDCs with this protocol resulted in enhanced migration, high NK-cell activation, and potent antigen-specific T-cell induction.We conclude that simultaneous activation of all BDC subsets with a combination of R848 + poly(I:C) generates highly immunostimulatory DCs. These results support further investigation and clinical testing, as standalone or in conjunction with other immunotherapeutic strategies including adoptive T-cell transfer and checkpoint inhibition.

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Natural Killer–Dendritic Cell Interactions in Liver Cancer: Implications for Immunotherapy

Cited by 23 publications

References 214 publications

Natural Killer Cells in SARS-CoV-2 Infection: Pathophysiology and Therapeutic Implications

Natural Killer Cells in SARS-CoV-2 Infection: Pathophysiology and Therapeutic Implications

A novel HCC prognosis predictor PDSS1 affects the cell cycle through the STAT3 signaling pathway in HCC

Blood DCs activated with R848 and poly(I:C) induce antigen-specific immune responses against viral and tumor-associated antigens

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