Molecular mechanisms of dendritic cell migration in immunity and cancer

Winde, Charlotte M. de; Munday, Clare; Acton, Sophie E.

doi:10.1007/s00430-020-00680-4

Cited by 60 publications

(60 citation statements)

References 184 publications

(265 reference statements)

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“…DCs are a heterogeneous population of professional antigen-presenting cells central to the induction and maintenance of adaptive immunity within tumor microenvironment 58 , 65 . In particular, two subsets of DCs exert the most potent antitumor functions, including conventional DCs type 1 (cDC1s) that stimulate T cell proliferation, and pDCs that produce interferon-α (IFN-α) 65 , 66 . cDC1s not only take up and cross-present tumor antigens via major histocompatibility complex (MHC) class I to activate naive CD8 + T cells; but also support the cytotoxicity of CD8 + T cells by secreting large amounts of interleukin-12 (IL-12).…”

Section: Discussionmentioning

confidence: 99%

“…cDC1s not only take up and cross-present tumor antigens via major histocompatibility complex (MHC) class I to activate naive CD8 + T cells; but also support the cytotoxicity of CD8 + T cells by secreting large amounts of interleukin-12 (IL-12). Then, activated cytotoxic CD8 + T cells migrate to tumors and kill them 65 . pCDs play two opposite roles in tumor immunity depending on their subsets via inducing Treg or activating cytotoxic T cells respectively 65 , 66 .…”

Section: Discussionmentioning

confidence: 99%

“…Then, activated cytotoxic CD8 + T cells migrate to tumors and kill them 65 . pCDs play two opposite roles in tumor immunity depending on their subsets via inducing Treg or activating cytotoxic T cells respectively 65 , 66 . Based on our result that PARD3 negatively correlated with DCs and cytotoxic T cells, we speculate that immune infiltration related to PARD3 may contribute to the unfavorable outcomes for HCC, yet the specific regulation mechanism needed to further elucidate.…”

Section: Discussionmentioning

confidence: 99%

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High expression of PARD3 predicts poor prognosis in hepatocellular carcinoma

Huang

Yang

et al. 2021

Sci Rep

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Hepatocellular carcinoma (HCC) is one of the most commonly cancers with poor prognosis and drug response. Identifying accurate therapeutic targets would facilitate precision treatment and prolong survival for HCC. In this study, we analyzed liver hepatocellular carcinoma (LIHC) RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA), and identified PARD3 as one of the most significantly differentially expressed genes (DEGs). Then, we investigated the relationship between PARD3 and outcomes of HCC, and assessed predictive capacity. Moreover, we performed functional enrichment and immune infiltration analysis to evaluate functional networks related to PARD3 in HCC and explore its role in tumor immunity. PARD3 expression levels in 371 HCC tissues were dramatically higher than those in 50 paired adjacent liver tissues (p < 0.001). High PARD3 expression was associated with poor clinicopathologic feathers, such as advanced pathologic stage (p = 0.002), vascular invasion (p = 0.012) and TP53 mutation (p = 0.009). Elevated PARD3 expression also correlated with lower overall survival (OS, HR = 2.08, 95% CI = 1.45–2.98, p < 0.001) and disease-specific survival (DSS, HR = 2.00, 95% CI = 1.27–3.16, p = 0.003). 242 up-regulated and 71 down-regulated genes showed significant association with PARD3 expression, which were involved in genomic instability, response to metal ions, and metabolisms. PARD3 is involved in diverse immune infiltration levels in HCC, especially negatively related to dendritic cells (DCs), cytotoxic cells, and plasmacytoid dendritic cells (pDCs). Altogether, PARD3 could be a potential prognostic biomarker and therapeutic target of HCC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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High expression of PARD3 predicts poor prognosis in hepatocellular carcinoma

Huang

Yang

et al. 2021

Sci Rep

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“…By these mechanisms, CR3-dependent binding and uptake of applied NC may be increased. However, at later time points after the onset of activation, in the case of professional APC like cDC, internalization of the material may cease as a consequence of the functional switch of the activated APC to emigrate towards secondary lymphoid organs to present (pathogen-) derived antigen to T cells [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

Complement-Opsonized Nano-Carriers Are Bound by Dendritic Cells (DC) via Complement Receptor (CR)3, and by B Cell Subpopulations via CR-1/2, and Affect the Activation of DC and B-1 Cells

Bednarczyk

Medina‐Montano

Fittler

et al. 2021

IJMS

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The development of nanocarriers (NC) for biomedical applications has gained large interest due to their potential to co-deliver drugs in a cell-type-targeting manner. However, depending on their surface characteristics, NC accumulate serum factors, termed protein corona, which may affect their cellular binding. We have previously shown that NC coated with carbohydrates to enable biocompatibility triggered the lectin-dependent complement pathway, resulting in enhanced binding to B cells via complement receptor (CR)1/2. Here we show that such NC also engaged all types of splenic leukocytes known to express CR3 at a high rate when NC were pre-incubated with native mouse serum resulting in complement opsonization. By focusing on dendritic cells (DC) as an important antigen-presenting cell type, we show that CR3 was essential for binding/uptake of complement-opsonized NC, whereas CR4, which in mouse is specifically expressed by DC, played no role. Further, a minor B cell subpopulation (B-1), which is important for first-line pathogen responses, and co-expressed CR1/2 and CR3, in general, engaged NC to a much higher extent than normal B cells. Here, we identified CR-1/2 as necessary for binding of complement-opsonized NC, whereas CR3 was dispensable. Interestingly, the binding of complement-opsonized NC to both DC and B-1 cells affected the expression of activation markers. Our findings may have important implications for the design of nano-vaccines against infectious diseases, which codeliver pathogen-specific protein antigen and adjuvant, aimed to induce a broad adaptive cellular and humoral immune response by inducing cytotoxic T lymphocytes that kill infected cells and pathogen-neutralizing antibodies, respectively. Decoration of nano-vaccines either with carbohydrates to trigger complement activation in vivo or with active complement may result in concomitant targeting of DC and B cells and thereby may strongly enhance the extent of dual cellular/humoral immune responses.

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“…Tetraspanins are involved in many aspects of immunity, and as such play a pivotal role in establishing an effective immune response [ 16 – 18 ]. Further overview articles in this special issue highlight that tetraspanins control different stages of the migration of dendritic cells, which engulf and present antigens to initiate an immune response, from the site of infection to the lymph node [ 19 ]. On mast cells, important in antiviral responses and hyperactive in patients with allergies, tetraspanins control release of intracellular granules with immunomodulatory compounds by membrane remodelling [ 20 ].…”

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confidence: 99%