ArticleOncoimmunology2012
Tumor-mediated inhibition of human dendritic cell differentiation and function is consistently counteracted by combined p38 MAPK and STAT3 inhibition.
Article in Oncoimmunology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 59 citations in OpenAlex.
- Decoding myeloid heterogeneity in glioblastoma: spatial insights from transcriptomics.Journal of translational medicine · 2026Review
- Insights of immune cell heterogeneity, tumor-initiated subtype transformation, drug resistance, treatment and detecting technologies in glioma microenvironment.Journal of advanced research · 2025Review
- Xiao Qing Long Tang ameliorates neutrophil extracellular trap-dendritic cells-T helper 17 cell axis in Neutrophilic Asthma.PloS one · 2025Article
- Guidelines for preparation and flow cytometry analysis of human nonlymphoid tissue DC.European journal of immunology · 2025Article
- The Dysregulation of the Monocyte-Dendritic Cell Interplay Is Associated with In-Hospital Mortality in COVID-19 Pneumonia.Journal of clinical medicine · 2024Article
- Biomaterials Facilitating Dendritic Cell-Mediated Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- Dendritic Cell Subsets in Melanoma: Pathophysiology, Clinical Prognosis and Therapeutic Exploitation.Cancers · 2023Review
- From simplicity to complexity in current melanoma models.Experimental dermatology · 2022Review
- Review
- MF59 Promoted the Combination of CpG ODN1826 and MUC1-MBP Vaccine-Induced Antitumor Activity Involved in the Enhancement of DC Maturation by Prolonging the Local Retention Time of Antigen and Down-Regulating of IL-6/STAT3.International journal of molecular sciences · 2022Article
- Inflammation and tumor progression: signaling pathways and targeted intervention.Signal transduction and targeted therapy · 2021Article
- Centrosome Dynamics and Its Role in Inflammatory Response and Metastatic Process.Biomolecules · 2021Review
- Postponing tumor onset and tumor progression can be achieved by alteration of local tumor immunity.Cancer cell international · 2021Article
- From Melanoma Development to RNA-Modified Dendritic Cell Vaccines: Highlighting the Lessons From the Past.Frontiers in immunology · 2021Review
- Micro-environmental cross-talk in an organotypic human melanoma-in-skin model directs M2-like monocyte differentiation via IL-10.Cancer immunology, immunotherapy : CII · 2020Article
- Breast cancer-induced immune suppression in the sentinel lymph node is effectively countered by CpG-B in conjunction with inhibition of the JAK2/STAT3 pathway.Journal for immunotherapy of cancer · 2020Article
- The non-linearity of RAF-MEK signaling in dendritic cells.Cell cycle (Georgetown, Tex.) · 2020Review
- Oncolytic adenovirus ORCA-010 increases the type 1 T cell stimulatory capacity of melanoma-conditioned dendritic cells.Clinical and experimental immunology · 2020Article
- Dendritic cells in cancer immunology and immunotherapy.Nature reviews. Immunology · 2020Review
- Immunosuppressive effects of tick protein RHcyst-1 on murine bone marrow-derived dendritic cells.Parasites & vectors · 2019Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Targeting dendritic cells (DC) through the release of suppressive factors is an effective means for tumors to escape immune control. We assessed the involvement of downstream signaling through the JAK2/STAT3 and p38 MAPK pathways in tumor-induced suppression of human DC development. Whereas the JAK2/STAT3 pathway has been pinpointed in mouse studies as a key regulator of myeloid suppression, in human DC this is less well established. We studied the effects of STAT3 inhibition on the suppression of monocyte-derived DC differentiation mediated by a short-list of four predominant suppressive factors and found that pharmacological STAT3 inhibition could only counteract the effects of IL-6. Accordingly, in testing a panel of supernatants derived from 11 cell lines representing various types of solid tumors, STAT3 inhibition only modestly affected the suppressive effects of a minority of supernatants. Importantly, combined interference in the STAT3 and p38 pathways completely prevented inhibition of DC differentiation by all tested supernatants and effected superior DC function, evidenced by increased allogeneic T cell reactivity with elevated IL-12p70/IL-10 ratios and Th1 skewing. Combined STAT3 and p38 inhibition also afforded superior protection against the suppressive effects of primary glioma and melanoma supernatants and induced a shift from CD14(+) cells to CD1a(+) cells in metastatic melanoma single-cell suspensions, indicating a potential for improved DC differentiation in the tumor microenvironment. We conclude that combined interference in the STAT3 and p38 MAPK signaling pathways is a promising approach to overcome tumor-induced inhibitory signaling in DC precursors and will likely support clinical immunotherapeutic strategies.
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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.