ArticleNature medicine2015
Selective inhibition of the p38 alternative activation pathway in infiltrating T cells inhibits pancreatic cancer progression.
Article in Nature medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
51 citing papers in PubMed, 66 citations in OpenAlex.
- Article
- The PIN1-p38-CtIP signalling axis protects stalled replication forks from deleterious degradation.Nucleic acids research · 2025Article
- Article
- The role of inflammatory factors in the tumor microenvironment of pancreatic cancer.Frontiers in immunology · 2025Review
- Targeting protein modification: a new direction for immunotherapy of pancreatic cancer.International journal of biological sciences · 2025Review
- Tumor-infiltrating mast cells confer resistance to immunotherapy in pancreatic cancer.iScience · 2024Article
- TNFR1 signaling promotes pancreatic tumor growth by limiting dendritic cell number and function.Cell reports. Medicine · 2024Article
- Current and future immunotherapeutic approaches in pancreatic cancer treatment.Journal of hematology & oncology · 2024Review
- Impact of GADD45A on Radiation Biodosimetry Using Mouse Peripheral Blood.Radiation research · 2023Article
- P38 kinase in gastrointestinal cancers.Cancer gene therapy · 2023Review
- IL-17A-producing CD8Gut · 2023Article
- Characterization of p38α autophosphorylation inhibitors that target the non-canonical activation pathway.Nature communications · 2023Article
- p38MAPKα Stromal Reprogramming Sensitizes Metastatic Breast Cancer to Immunotherapy.Cancer discovery · 2023Article
- DAPTA, a C-C Chemokine Receptor 5 (CCR5), Leads to the Downregulation of Notch/NF-κB Signaling and Proinflammatory Mediators in CD40Biomedicines · 2023Article
- Effect of the p38 Mitogen-Activated Protein Kinase Signaling Cascade on Radiation Biodosimetry.Radiation research · 2022Article
- Small Molecule Signatures of Mice Lacking T-cell p38 Alternate Activation, a Model for Immunosuppression Conditions, after Total-Body Irradiation.Radiation research · 2022Article
- GADD45 in Stress Signaling, Cell Cycle Control, and Apoptosis.Advances in experimental medicine and biology · 2022Article
- Thyroid hormones act as modulators of inflammation through their nuclear receptors.Frontiers in endocrinology · 2022Review
- PCAT19 Regulates the Proliferation and Apoptosis of Lung Cancer Cells by Inhibiting miR-25-3p via Targeting the MAP2K4 Signal Axis.Disease markers · 2022Article
- Gadd45 Proteins in Immunity 2.0.Advances in experimental medicine and biology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive neoplasm characterized by a marked fibro-inflammatory microenvironment, the presence of which can promote both cancer induction and growth. Therefore, selective manipulation of local cytokines is an attractive, although unrealized, therapeutic approach. T cells possess a unique mechanism of p38 mitogen-activated protein kinase (MAPK) activation downstream of T cell receptor (TCR) engagement through the phosphorylation of Tyr323 (pY323). This alternative p38 activation pathway is required for pro-inflammatory cytokine production. Here we show in human PDAC that a high percentage of infiltrating pY323(+) T cells was associated with large numbers of tumor necrosis factor (TNF)-α- and interleukin (IL)-17-producing CD4(+) tumor-infiltrating lymphocytes (TILs) and aggressive disease. The growth of mouse pancreatic tumors was inhibited by genetic ablation of the alternative p38 pathway, and transfer of wild-type CD4(+) T cells, but not those lacking the alternative pathway, enhanced tumor growth in T cell-deficient mice. Notably, a plasma membrane-permeable peptide derived from GADD45-α, the naturally occurring inhibitor of p38 pY323(+) (ref. 7), reduced CD4(+) TIL production of TNF-α, IL-17A, IL-10 and secondary cytokines, halted growth of implanted tumors and inhibited progression of spontaneous KRAS-driven adenocarcinoma in mice. Thus, TCR-mediated activation of CD4(+) TILs results in alternative p38 activation and production of protumorigenic factors and can be targeted for therapeutic benefit.
Indexed as
Identifiers
What OpenQuestion holds
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.