ArticleCancer immunology, immunotherapy : CII2016
IL-6 down-regulates HLA class II expression and IL-12 production of human dendritic cells to impair activation of antigen-specific CD4(+) T cells.
Article in Cancer immunology, immunotherapy : CII, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 111 citations in OpenAlex.
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- Adaptive resistance in cancer immunotherapy.Cellular & molecular immunology · 2026Review
- IL‑6: A key player in the EGFR‑TKI‑resistant tumor microenvironment and its therapeutic implications (Review).International journal of oncology · 2026Review
- <p>Tumor microenvironment in bone sarcomas: Implications for immunotherapy and emerging therapeutic vulnerabilities (Review)</p>.Oncology reports · 2026Review
- DNA methylation-mediated silencing of MEOX1 promotes glycolysis and immune evasion in colorectal cancer cells through inhibition of GLP2R transcription.Cell & bioscience · 2026Article
- Genome-wide H3K4me3 profiling of circulating immune cells reveals dynamic epigenetic reprogramming during acute critical COVID-19.Frontiers in immunology · 2026Article
- Pro-inflammatory monocytes in patients with calcific aortic valve disease.Cardiovascular research · 2025Article
- Safety Assessment of Stem Cell-Based Therapies: Current Standards and Advancing Frameworks.Cells · 2025Review
- Role of interleukin-6 in resistance to tumor therapy.Discover oncology · 2025Review
- IL-6 is a prognostic biomarker in patients with advanced esophageal squamous cell carcinoma received with PD-1 inhibitors.Frontiers in immunology · 2025Article
- Immunophenotyping of septic shock patients with endotheliopathy: focus on monocyte subtypes and Immune regulatory molecules.Frontiers in immunology · 2025Article
- Dendritic cells in multiple myeloma: from immune evasion to therapeutic potential.Frontiers in immunology · 2025Review
- Advances in Interleukin-6 Family Cytokines and the Role in Respiratory Diseases.Journal of inflammation research · 2025Review
- Extrachromosomal circular DNA and their roles in cancer progression.Genes & diseases · 2025Review
- The dichotomic role of cytokines in aging.Biogerontology · 2024Review
- Targeting cytokine and chemokine signaling pathways for cancer therapy.Signal transduction and targeted therapy · 2024Review
- RNAi mediated silencing of STAT3/PD-L1 in tumor-associated immune cells induces robust anti-tumor effects in immunotherapy resistant tumors.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
14 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immunosuppression in tumor microenvironments critically affects the success of cancer immunotherapy. Here, we focused on the role of interleukin (IL)-6/signal transducer and activator of transcription (STAT3) signaling cascade in immune regulation by human dendritic cells (DCs). IL-6-conditioned monocyte-derived DCs (MoDCs) impaired the presenting ability of cancer-related antigens. Interferon (IFN)-γ production attenuated by CD4(+) T cells co-cultured with IL-6-conditioned MoDCs corresponded with decreased DC IL-12p70 production. Human leukocyte antigen (HLA)-DR and CD86 expression was significantly reduced in CD11b(+)CD11c(+) cells obtained from peripheral blood mononuclear cells (PBMCs) of healthy donors by IL-6 treatment and was STAT3 dependent. Arginase-1 (ARG1), lysosomal protease, cathepsin L (CTSL), and cyclooxygenase-2 (COX2) were involved in the reduction of surface HLA-DR expression. Gene expressions of ARG1, CTSL, COX2, and IL6 were higher in tumor-infiltrating CD11b(+)CD11c(+) cells compared with PBMCs isolated from colorectal cancer patients. Expression of surface HLA-DR and CD86 on CD11b(+)CD11c(+) cells was down-regulated, and T cell-stimulating ability was attenuated compared with PBMCs, suggesting that an immunosuppressive phenotype might be induced by IL-6, ARG1, CTSL, and COX2 in tumor sites of colorectal cancer patients. There was a relationship between HLA-DR expression levels in tumor tissues and the size of CD4(+) T and CD8(+) T cell compartments. Our findings indicate that IL-6 causes a dysfunction in human DCs that activates cancer antigen-specific Th cells, suggesting that blocking the IL-6/STAT3 signaling pathway might be a promising strategy to improve cancer immunotherapy.
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