Dendritic cell subsets and locations

Balan, Sreekumar; Saxena, Mansi; Bhardwaj, Nina

doi:10.1016/bs.ircmb.2019.07.004

Cited by 234 publications

(195 citation statements)

References 314 publications

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“…[69][70][71] Initially, it has been proposed that the engulfment of dying cancer cells by tumor-infiltrating CD8α + DCs would trigger STING signaling in the latter, culminating in the abundant secretion of type I IFN and consequent activation of autocrine and paracrine pathways supporting the crosspriming of tumor-specific CD8 + cytotoxic T lymphocytes (CTLs). [72][73][74][75][76][77][78][79] Consistent with this model, Sting1 −/mice are unable to mount efficient T cell immunity against syngeneic melanomas 57 and gliomas, 80 correlating with deficient type I IFN production. Similarly, Goldenticket mice -which harbor a single nucleotide polymorphism in Sting1 (T596A) that mimics the effects of a loss-of-function mutation -cannot establish efficient IFN-dependent immune responses against Listeria monocytogenes.…”

Section: Sting Signaling In Preclinical Tumor Modelsmentioning

confidence: 55%

Trial watch: STING agonists in cancer therapy

et al. 2020

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Stimulator of interferon response cGAMP interactor 1 (STING1, best known as STING) is an endoplasmic reticulum-sessile protein that serves as a signaling hub, receiving input from several pattern recognition receptors, most of which sense ectopic DNA species in the cytosol. In particular, STING ensures the production of type I interferon (IFN) in response to invading DNA viruses, bacterial pathogens, as well as DNA leaking from mitochondria or the nucleus (e.g., in cells exposed to chemotherapy or radiotherapy). As a type I IFN is critical for the initiation of anticancer immune responses, the pharmaceutical industry has generated molecules that directly activate STING for use in oncological indications. Such STING agonists are being tested in clinical trials with the rationale of activating STING in tumor cells or tumor-infiltrating immune cells (including dendritic cells) to elicit immunostimulatory effects, alone or in combination with a range of established chemotherapeutic and immunotherapeutic regimens. In this Trial Watch, we discuss preclinical evidence and accumulating clinical experience shaping the design of Phase I and Phase II trials that evaluate the safety and preliminary efficacy of STING agonists in cancer patients.

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Section: Sting Signaling In Preclinical Tumor Modelsmentioning

confidence: 55%

Trial watch: STING agonists in cancer therapy

et al. 2020

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“…Masud Alam and collaborators (National Cancer Institute, Frederick, MD, USA) showed that the TH1-polarizing alarm high mobility group nucleosome binding domain 1 (HMGN1) and resiquimod synergize at driving the functional maturation of human monocyte-derived DCs (MoDCs) and mouse bone marrow-derived DCs (BMDCs), 93 which is accompanied by NF-κB activation, 92 upregulation of DC surface proteins including CD80, CD83, CD86, and HLA-DR, and production of pro-inflammatory cytokines such as interleukin (IL)-12, IL-1β, and tumor necrosis factor (TNF). 92 Moreover, HMGN1 and resiquimod were found to synergize at triggering the nuclear translocation of interferon regulatory factor 3 (IRF3) and IRF7, 92 and hence at driving the secretion of type I IFN from DCs.…”

Section: Recent Preclinical Developmentsmentioning

confidence: 99%

Trial Watch: experimental TLR7/TLR8 agonists for oncological indications

Frega

Naour

et al. 2020

OncoImmunology

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Resiquimod (R848) and motolimod (VTX-2337) are second-generation experimental derivatives of imiquimod, an imidazoquinoline with immunostimulatory properties originally approved by the US Food and Drug Administration for the topical treatment of actinic keratosis and genital warts more than 20 years ago. Both resiquimod and motolimod operate as agonists of Toll-like receptor 7 (TLR7) and/or TLR8, in thus far delivering adjuvant-like signals to antigen-presenting cells (APCs). In line with such an activity, these compounds are currently investigated as immunostimulatory agents for the treatment of various malignancies, especially in combination with peptide-based, dendritic cell-based, cancer cell lysate-based, or DNA-based vaccines. Here, we summarize preclinical and clinical evidence recently collected to support the development of resiquimod and motolimod and other TLR7/TLR8 agonists as anticancer agents.

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“…Tumor infiltrating cDCs show a dynamic distribution over time and can influence disease progression at different stages of tumor growth [150,151]. For instance, increased cDC infiltration was associated in early pancreatic ductal adenocarcinoma (PDAC) lesions with better anti-tumor immunity of CD8 + T cells and in advanced PDAC, with increased efficacy of radiation therapy [152].…”

Section: Prognostic Value Of DC Subsets In Tmementioning

confidence: 99%

Functional Role of Dendritic Cell Subsets in Cancer Progression and Clinical Implications

Prete

Sozio

Barbazza

et al. 2020

IJMS

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Dendritic cells (DCs) constitute a complex network of cell subsets with common functions but also with many divergent aspects. All dendritic cell subsets share the ability to prime T cell response and to undergo a complex trafficking program related to their stage of maturation and function. For these reasons, dendritic cells are implicated in a large variety of both protective and detrimental immune responses, including a crucial role in promoting anti-tumor responses. Although cDC1s are the most potent subset in tumor antigen cross-presentation, they are not sufficient to induce full-strength anti-tumor cytotoxic T cell response and need close interaction and cooperativity with the other dendritic cell subsets, namely cDC2s and pDCs. This review will take into consideration different aspects of DC biology, including the functional role of dendritic cell subsets in both fostering and suppressing tumor growth, the mechanisms underlying their recruitment into the tumor microenvironment, as well as the prognostic value and the potentiality of dendritic cell therapeutic targeting. Understanding the specificity of dendritic cell subsets will allow to gain insights on role of these cells in pathological conditions and to design new selective promising therapeutic approaches.

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Dendritic cell subsets and locations

Cited by 234 publications

References 314 publications

Trial watch: STING agonists in cancer therapy

Trial watch: STING agonists in cancer therapy

Trial Watch: experimental TLR7/TLR8 agonists for oncological indications

Functional Role of Dendritic Cell Subsets in Cancer Progression and Clinical Implications

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