ArticleBlood2021
Overcoming T-cell exhaustion in LCH: PD-1 blockade and targeted MAPK inhibition are synergistic in a mouse model of LCH.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 48 citations in OpenAlex.
- Article
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- [Immune microenvironment of Langerhans cell histiocytosis: from immune suppression to targeted therapy].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2025Review
- Retrospective nationwide survey of pediatric RDD in Japan: a high prevalence of mutations in the kinase pathway genes.International journal of hematology · 2025Article
- Disease response criteria in Langerhans cell histiocytosis: a global view.International journal of hematology · 2025Review
- High CCR6 expression increases the risk of pediatric Langerhans cell histiocytosis.Blood science (Baltimore, Md.) · 2025Article
- PCSK9 in T-cell function and the immune response.Biomarker research · 2024Review
- Role of PD-1/PD-L1 signaling axis in oncogenesis and its targeting by bioactive natural compounds for cancer immunotherapy.Military Medical Research · 2024Review
- Langerhans cell histiocytosis: NACHO update on progress, chaos, and opportunity on the path to rational cures.Cancer · 2024Review
- Adverse clinical outcomes and immunosuppressive microenvironment of RHO-GTPase activation pattern in hepatocellular carcinoma.Journal of translational medicine · 2024Article
- Clinical features and prognostic factors of pediatric Langerhans cell histiocytosis: a single-center retrospective study.Frontiers in medicine · 2024Article
- Circulating senescent myeloid cells infiltrate the brain and cause neurodegeneration in histiocytic disorders.Immunity · 2023Article
- Langerhans cell histiocytosis: promises and caveats of targeted therapies in high-risk and CNS disease.Hematology. American Society of Hematology. Education Program · 2023Review
- Children's Oncology Group's 2023 blueprint for research: Non-Hodgkin lymphoma.Pediatric blood & cancer · 2023Article
- Clinicogenomic associations in childhood Langerhans cell histiocytosis: an international cohort study.Blood advances · 2023Article
- Langerhans cell histiocytosis: current advances in molecular pathogenesis.Frontiers in immunology · 2023Review
- Expression and Clinical Correlation of PD-1/PD-L1 and VE1(BRAFp.V600E) in Pediatric Langerhans Cell Histiocytosis.Mediterranean journal of hematology and infectious diseases · 2023Article
- Detection of Immune Microenvironment Changes and Immune-Related Regulators in Langerhans Cell Histiocytosis Bone Metastasis.BioMed research international · 2023Article
- Signaling pathways, microenvironment, and targeted treatments in Langerhans cell histiocytosis.Cell communication and signaling : CCS · 2022Review
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Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
Abstract
Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia characterized by granulomatous lesions containing pathological CD207+ dendritic cells (DCs) with persistent MAPK pathway activation. Standard-of-care chemotherapies are inadequate for most patients with multisystem disease, and optimal strategies for relapsed and refractory disease are not defined. The mechanisms underlying development of inflammation in LCH lesions, the role of inflammation in pathogenesis, and the potential for immunotherapy are unknown. Analysis of the immune infiltrate in LCH lesions identified the most prominent immune cells as T lymphocytes. Both CD8+ and CD4+ T cells exhibited "exhausted" phenotypes with high expression of the immune checkpoint receptors. LCH DCs showed robust expression of ligands to checkpoint receptors. Intralesional CD8+ T cells showed blunted expression of Tc1/Tc2 cytokines and impaired effector function. In contrast, intralesional regulatory T cells demonstrated intact suppressive activity. Treatment of BRAFV600ECD11c LCH mice with anti-PD-1 or MAPK inhibitor reduced lesion size, but with distinct responses. Whereas MAPK inhibitor treatment resulted in reduction of the myeloid compartment, anti-PD-1 treatment was associated with reduction in the lymphoid compartment. Notably, combined treatment with MAPK inhibitor and anti-PD-1 significantly decreased both CD8+ T cells and myeloid LCH cells in a synergistic fashion. These results are consistent with a model that MAPK hyperactivation in myeloid LCH cells drives recruitment of functionally exhausted T cells within the LCH microenvironment, and they highlight combined MAPK and checkpoint inhibition as a potential therapeutic strategy.
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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.