ArticleJournal for immunotherapy of cancer2021
p38 MAPK signaling in M1 macrophages results in selective elimination of M2 macrophages by MEK inhibition.
Article in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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
30 citing papers in PubMed, 46 citations in OpenAlex.
- Regression-Associated Macrophages Recruit Natural Killer Cells That Constrain Targeted Therapy Resistance.Cancer research · 2026Article
- Leptin-induced autophagy regulates the immunomodulatory potential of adipose-derived mesenchymal stem cells through down regulating the expression of TSG-6.Scientific reports · 2026Article
- P38MAPK targeting in pancreatic ductal adenocarcinoma: Promising interventional approach for breaking drug resistance and tumor control.Medical oncology (Northwood, London, England) · 2026Article
- EBF3 suppresses lung adenocarcinoma progression and immune evasion via transcriptional repression of CCL24.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Dissection of the T cell infiltrate in mouse pancreatic tumors reveals an extensive and diverse tumor-reactive T cell repertoire.Science advances · 2026Article
- Review
- Targeting Triple-Negative Breast Cancer with Momordicine-I for Therapeutic Gain in Preclinical Models.Cancers · 2025Article
- Enhancing radiotherapy-induced anti-tumor immunity via nanoparticle-mediated STING agonist synergy.Molecular cancer · 2025Review
- Delineation of signaling routes that underlie differences in macrophage phenotypic states.NAR molecular medicine · 2025Article
- Modulating M1/M2 macrophage polarization with plant metabolites: a therapeutic strategy for rheumatoid arthritis.Frontiers in pharmacology · 2025Review
- L-arginine-loaded microneedle patch enhances diabetic wound healing by regulating macrophage polarisation and mitochondrial homeostasis.Regenerative biomaterials · 2025Article
- Distinct mechanisms of type 3 secretion system recognition control LTB4 synthesis in neutrophils and macrophages.PLoS pathogens · 2024Article
- MAP kinase kinase 1 (MEK1) within extracellular vesicles inhibits tumour growth by promoting anti-tumour immunity.Journal of extracellular vesicles · 2024Article
- Trem2 acts as a non-classical receptor of interleukin-4 to promote diabetic wound healing.Clinical and translational medicine · 2024Article
- Adipose-derived stem cell exosomes loaded with icariin alleviates rheumatoid arthritis by modulating macrophage polarization in rats.Journal of nanobiotechnology · 2024Article
- Distinct Mechanisms of Type 3 Secretion System Recognition Control LTBbioRxiv : the preprint server for biology · 2024Article
- THP-1 Monocytic Cells Are Polarized to More Antitumorigenic Macrophages by Serial Treatment with Phorbol-12-Myristate-13-Acetate and PD98059.Medicina (Kaunas, Lithuania) · 2024Article
- Role of Histone Deacetylase Inhibitor in Diabetic Painful Neuropathy.Molecular neurobiology · 2024Article
- Targeting endoplasmic reticulum associated degradation pathway combined with radiotherapy enhances the immunogenicity of esophageal cancer cells.Cancer biology & therapy · 2023Article
- Dual-Specificity Phosphatases in Regulation of Tumor-Associated Macrophage Activity.International journal of molecular sciences · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
M2 macrophages promote tumor progression and therapy resistance, whereas proimmunogenic M1 macrophages can contribute to the efficacy of cytostatic and immunotherapeutic strategies. The abundance of M2 macrophages in the immune infiltrate of many cancer types has prompted the search for strategies to target and eliminate this subset. From our prior experiments in syngeneic mouse tumor models, we learned that pharmacological inhibition of mitogen-activated protein kinase kinase (MEK) did not merely result in tumor cell death, but also in the modulation of the tumor immune infiltrate. This included a prominent decrease in the numbers of macrophages as well as an increase in the M1/M2 macrophage ratio. Investigation of the mechanism underlying this finding in primary murine macrophage cultures revealed that M2 macrophages are significantly more sensitive to MEK inhibition-induced cell death than their M1 counterparts. Further analyses showed that the p38 MAPK pathway, which is activated in M1 macrophages only, renders these cells resistant to death by MEK inhibition. In conclusion, the dependency of M2 macrophages on the MEK/extracellular-signal regulated kinase (ERK) pathway empowers MEK inhibitors to selectively eliminate this subset from the tumor microenvironment.
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.