Observational studyJCI insight2021
PLA2G4A promotes right-sided colorectal cancer progression by inducing CD39+γδ Treg polarization.
Observational study in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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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.
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Who cites it
33 citing papers in PubMed, 46 citations in OpenAlex.
- γδ T cells and cancer.The Journal of clinical investigation · 2026Review
- γδ T cells in colorectal and liver cancer.Nature reviews. Gastroenterology & hepatology · 2026Review
- The Phospholipase AJournal of lipid and atherosclerosis · 2026Review
- Integrated Spatial and Bulk Untargeted Metabolomics Characterize Location- and Histology-Associated Metabolic Heterogeneity in Colorectal Cancer.Journal of proteome research · 2026Article
- cPLA2α inhibition potentiates anti-PD-1 immunotherapy in lung adenocarcinoma via remodeling tumor microenvironment.Communications biology · 2026Article
- The Immunomodulatory Effects of Porcupine Bezoar on Cyclophosphamide-Induced Immunosuppression in Rats.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Tumor-intrinsic metabolic pathways essential for tumorigenesis and resistance to anti-PD1 in oncogenic Kras-driven lung adenocarcinoma.Cancer & metabolism · 2026Article
- Pirin Transcriptionally Regulates PLA2G4A To Inhibit Ferroptosis in Colorectal Cancer via Lipid Profile Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- CD39 and CD73: biological functions, diseases and therapy.Molecular biomedicine · 2025Review
- The role of lipid metabolic interactions in reshaping the tumor microenvironment.Acta biochimica et biophysica Sinica · 2025Article
- Does side matter? Deciphering mechanisms that underpin side-dependent pathogenesis and therapy response in colorectal cancer.Molecular cancer · 2025Review
- A prognostic model for multiple myeloma based on lipid metabolism related genes.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Article
- scRNA-seq reveals that VEGF signaling mediates the response to neoadjuvant anlotinib combined with PD-1 blockade therapy in non-small cell lung cancer.Journal of translational medicine · 2025Article
- Regulating arachidonic acid metabolism: a novel strategy to prevent colorectal inflammatory cancer transformation.Journal of Cancer · 2025Review
- Progress of research on γδ T cells in colorectal cancer (Review).Oncology reports · 2024Review
- Link between mutations inWorld journal of gastrointestinal surgery · 2024Article
- TGF-β1 induces PD-1 expression in macrophages through SMAD3/STAT3 cooperative signaling in chronic inflammation.JCI insight · 2024Article
- Article
- Controversial role of γδ T cells in colorectal cancer.American journal of cancer research · 2024Review
- Spatiotemporal genomic profiling of intestinal metaplasia reveals clonal dynamics of gastric cancer progression.Cancer cell · 2023Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The γδ T cell is a promising candidate cell in tumor immunotherapy. However, γδ T cells polarize to CD39+γδ Tregs upon colorectal cancer (CRC) induction, and the underlying mechanism remains unclear. Here, we show that the frequency of CD39+γδ Tregs, which positively correlated with poor prognosis, was significantly higher in right-sided CRC (RSCRC) than in the left-sided CRC (LSCRC). Interestingly, CD39+γδ Tregs from RSCRC showed stronger immunosuppressive phenotype and function than LSCRC. Furthermore, the quantitative mass spectrometry data show that CD39+γδ Treg polarization was related to the abnormal activation of the Phospholipase a2-IVa/Arachidonic acid (PLA2G4A/AA) metabolic pathway in RSCRC. Using an in vitro coculture system and an orthotopic murine model of CRC, we show that the overexpression of Pla2g4a in CT26 cells induced CD39+γδ Tregs, inhibiting the antitumor immune response. Finally, we found that the overall survival of the PLA2G4Ahi group was significantly shortened compared with PLA2G4Alo RSCRC, while the survival of LSCRC showed the opposite. Collectively, RSCRC with abnormal PLA2G4A expression educates γδ T cells into CD39+γδ Tregs to promote tumor progression and metastasis. Our work highlights the interaction between cancer cells and immune cells by distinguishing the primary tumor site and deepens the understanding of the tumor microenvironment and immunosuppression.
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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.