ArticleJournal of immunotherapy (Hagerstown, Md. : 1997)2009
IL-4 suppresses very late antigen-4 expression which is required for therapeutic Th1 T-cell trafficking into tumors.
Article in Journal of immunotherapy (Hagerstown, Md. : 1997), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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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
20 citing papers in PubMed, 34 citations in OpenAlex.
- Long-Term Suppression of Circulating Proinflammatory Cytokines in Multiple Sclerosis Patients Following Autologous Haematopoietic Stem Cell Transplantation.Frontiers in immunology · 2021Trial
- Peptide vaccine immunotherapy biomarkers and response patterns in pediatric gliomas.JCI insight · 2018Trial
- Induction of robust type-I CD8+ T-cell responses in WHO grade 2 low-grade glioma patients receiving peptide-based vaccines in combination with poly-ICLC.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Trial
- Dual implication of endothelial adhesion molecules in tumor progression and cancer immunity.Cell adhesion & migration · 2025Review
- Exploring the regulatory mechanisms of paraptosis-related prognostic genes in gastric cancer using single-cell sequencing and transcriptome analysis.Scientific reports · 2025Article
- IL-4 impairs the formation of skin-resident memory CD8Nature immunology · 2025Article
- High LYRM4-AS1 predicts poor prognosis in patients with glioma and correlates with immune infiltration.PeerJ · 2023Article
- High-grade glioma associated immunosuppression does not prevent immune responses induced by therapeutic vaccines in combination with TCancer immunology, immunotherapy : CII · 2018Article
- T-lymphocyte homing: an underappreciated yet critical hurdle for successful cancer immunotherapy.Laboratory investigation; a journal of technical methods and pathology · 2017Review
- NF-κB Pathways in the Pathogenesis of Multiple Sclerosis and the Therapeutic Implications.Frontiers in molecular neuroscience · 2016Review
- GM-CSF promotes the immunosuppressive activity of glioma-infiltrating myeloid cells through interleukin-4 receptor-α.Cancer research · 2013Article
- Dendritic cell vaccination in pediatric gliomas: lessons learnt and future perspectives.Frontiers in pediatrics · 2013Review
- IL-4 attenuates Th1-associated chemokine expression and Th1 trafficking to inflamed tissues and limits pathogen clearance.PloS one · 2013Article
- Synergy between CD8 T cells and Th1 or Th2 polarised CD4 T cells for adoptive immunotherapy of brain tumours.PloS one · 2013Article
- Nitric oxide inhibits the accumulation of CD4+CD44hiTbet+CD69lo T cells in mycobacterial infection.European journal of immunology · 2012Article
- Antibody to α4 integrin suppresses natural killer cells infiltration in central nervous system in experimental autoimmune encephalomyelitis.Journal of neuroimmunology · 2012Article
- MicroRNAs and STAT interplay.Seminars in cancer biology · 2012Review
- A therapeutic OX40 agonist dynamically alters dendritic, endothelial, and T cell subsets within the established tumor microenvironment.Cancer research · 2010Article
- Essential roles of VLA-4 in the hematopoietic system.International journal of hematology · 2010Review
- miR-17-92 expression in differentiated T cells - implications for cancer immunotherapy.Journal of translational medicine · 2010Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Murine CD4 T cells cultured under type 1 polarizing conditions selectively express significantly higher levels of the very late antigen (VLA)-4 and VLA-6 integrins when compared with T cells cultured under type 2 or nonpolarizing (type 0) conditions. This difference appears due to the action of interleukin (IL)-4, as loss of VLA-4/-6 expression on Th cells was prevented by inclusion of neutralizing anti-IL-4 mAb during the initial culture period. We also observed that CD4 T cells deficient in Stat6, a critical component of the IL-4R signaling cascade, retained high levels of VLA-4 and VLA-6 expression, regardless of IL-4 status in the culture conditions. When applied to committed Th1 cells, rIL-4 readily inhibited VLA-4 and VLA-6 expression to levels observed for Th2 cells, without altering the type 1 functional status of these cells. Conversely, low levels of VLA-4/VLA-6 expressed by committed Th2 cells could not be resurrected by culture in the presence of the Th1-kines IL-12p70 and interferon-gamma. Predictably, among the Th populations evaluated, Th1 cells alone adhered efficiently to, and were costimulated by, plate-bound VCAM-1 and laminin in a VLA-4-dependent or VLA-6-dependent manner, respectively. Finally, adoptive-transferred Th1 (but not Th2) cells developed from OT-II mice were uniquely competent to traffick into OVA M05 melanoma lesions in vivo, thereby enhancing the therapeutic benefits associated with cotransferred OVA-specific type 1 CD8 (OT-I) cells. These data suggest that treatment strategies capable of sustaining/enhancing VLA-4/VLA-6 expression on Th1 effector cells may yield improved clinical efficacy in the cancer setting.
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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.