ArticleThe Journal of investigative dermatology2014
Alternative activation of human plasmacytoid DCs in vitro and in melanoma lesions: involvement of LAG-3.
Article in The Journal of investigative dermatology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 92 citations in OpenAlex.
- In or out of control: Modulating regulatory T cell homeostasis and function with immune checkpoint pathways.Frontiers in immunology · 2022Pooled it
- Depletion of LAG-3Clinical pharmacology and therapeutics · 2021Trial
- Post-translational modifications of immune checkpoints: molecular mechanisms, tumor microenvironment remodeling, and therapeutic implications.Journal of biomedical science · 2026Review
- The role of coinhibitory receptor-expressing non-T cells in inflammation and immunity: unsung heroes or peripheral players?Experimental & molecular medicine · 2025Review
- Multi-engineered T cell vaccine boosting TCR-T cell therapy enhances anti-tumor function and eradicates heterogeneous solid tumors.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Brucella abortus impairs T lymphocyte responsiveness by mobilizing IL-1RA-secreting omental neutrophils.Nature communications · 2025Article
- Post-translational governance of NF-κB in cancer immunity: mechanisms and therapeutic horizons.Frontiers in immunology · 2025Review
- Overview of dendritic cells subsets and their involvement in immune-related pathological disease.BioImpacts : BI · 2025Review
- Nanobodies as innovative immune checkpoint modulators: advancing cancer immunotherapy.Medical oncology (Northwood, London, England) · 2024Review
- Targeting the NF-κB pathway as a potential regulator of immune checkpoints in cancer immunotherapy.Cellular and molecular life sciences : CMLS · 2024Review
- Synergistic combination therapy using cowpea mosaic virus intratumoral immunotherapy and Lag-3 checkpoint blockade.Cancer immunology, immunotherapy : CII · 2024Article
- Immunotherapy in melanoma: advances, pitfalls, and future perspectives.Frontiers in molecular biosciences · 2024Review
- LAG3 immune inhibitors: a novel strategy for melanoma treatment.Frontiers in oncology · 2024Review
- Advances in immune checkpoint-based immunotherapies for multiple sclerosis: rationale and practice.Cell communication and signaling : CCS · 2023Review
- Emerging roles of plasmacytoid dendritic cell crosstalk in tumor immunity.Cancer biology & medicine · 2023Review
- Targeting LAG-3, TIM-3, and TIGIT for cancer immunotherapy.Journal of hematology & oncology · 2023Review
- Role of Next Generation Immune Checkpoint Inhibitor (ICI) Therapy in Philadelphia Negative Classic Myeloproliferative Neoplasm (MPN): Review of the Literature.International journal of molecular sciences · 2023Review
- LAG-3 Inhibitors: Novel Immune Checkpoint Inhibitors Changing the Landscape of Immunotherapy.Biomedicines · 2023Review
- Beyond CTLA-4 and PD-1 Inhibition: Novel Immune Checkpoint Molecules for Melanoma Treatment.Cancers · 2023Review
- Dendritic Cell Subsets in Melanoma: Pathophysiology, Clinical Prognosis and Therapeutic Exploitation.Cancers · 2023Review
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Plasmacytoid dendritic cells (pDCs) at tumor sites are often tolerogenic. Although pDCs initiate innate and adaptive immunity upon Toll-like receptor (TLR) triggering by pathogens, TLR-independent signals may be responsible for pDC activation and immune suppression in the tumor inflammatory environment. To identify molecules that are potentially involved in alternative pDC activation, we explored the expression and function of lymphocyte activation gene 3 (LAG-3) in human pDCs. In this report, we showed the expression of LAG-3 on the cell surface of a subset of circulating human pDCs. LAG-3+ pDCs exhibited a partially mature phenotype and were enriched at tumor sites in samples from melanoma patients. We found that LAG-3 interacted with major histocompatibility complex class II (MHC-II) to induce TLR-independent activation of pDCs with limited IFNα and enhanced IL-6 production. This in vitro cytokine profile of LAG-3-activated pDCs paralleled that of tumor-associated pDCs analyzed ex vivo. By confocal microscopy, LAG-3+ pDCs detected in melanoma-invaded lymph nodes (LNs) stained positive for IL-6 and preferentially localized near melanoma cells. These results suggest that LAG-3-mediated activation of pDCs takes place in vivo at tumor sites, and it is in part responsible for directing an immune-suppressive environment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.