ArticleJournal for immunotherapy of cancer2018
1-Pyrroline-5-carboxylate released by prostate Cancer cell inhibit T cell proliferation and function by targeting SHP1/cytochrome c oxidoreductase/ROS Axis.
Article in Journal for immunotherapy of cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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
35 citing papers in PubMed, 78 citations in OpenAlex.
- Identification of a diagnostic metabolomic fingerprint in plasma for eosinophilic granulomatosis with polyangiitis.PloS one · 2026Article
- Integrative multi-omics analysis proposes a metabolic classification of gliomas: distinct metabolic states, immune infiltration, and prognosis.Journal of translational medicine · 2025Article
- Proline Metabolism in Cancer: Emerging Roles in Redox Homeostasis and Therapeutic Opportunities.Cancers · 2025Review
- Article
- Cellular Signaling of Amino Acid Metabolism in Prostate Cancer.International journal of molecular sciences · 2025Review
- Immune and Metabolic Reprogramming Induced by Paclitaxel, Capecitabine and Eribulin in Breast Cancer: Insights into Therapeutic Targets.Breast cancer (Dove Medical Press) · 2025Article
- Klotho enhances stability of chronic kidney disease atherosclerotic plaques by inhibiting GRK2/PLC-β-mediated endoplasmic reticulum stress in macrophages via modulation of the ROS/SHP1 pathway.Scientific reports · 2024Article
- Harnessing the tumor microenvironment to boost adoptive T cell therapy with engineered lymphocytes for solid tumors.Seminars in immunopathology · 2024Review
- Sirtuin 2 regulates neutrophil functions through NADiScience · 2024Article
- Deciphering glutamine metabolism patterns for malignancy and tumor microenvironment in clear cell renal cell carcinoma.Clinical and experimental medicine · 2024Article
- Review
- Photodynamic Therapy and Adaptive Immunity Induced by Reactive Oxygen Species: Recent Reports.Cancers · 2024Review
- 1-Pyrroline-5-carboxylate inhibit T cell glycolysis in prostate cancer microenvironment by SHP1/PKM2/LDHB axis.Cell communication and signaling : CCS · 2024Article
- Crosstalk between lactate and tumor-associated immune cells: clinical relevance and insight.Frontiers in oncology · 2024Review
- The Role of Tumor Metabolic Reprogramming in Tumor Immunity.International journal of molecular sciences · 2023Review
- Review
- Construction of the metabolism-related models for predicting prognosis and infiltrating immune phenotype in lung squamous cell carcinoma.Journal of Cancer · 2023Article
- Can proline dehydrogenase-a key enzyme involved in proline metabolism-be a novel target for cancer therapy?Frontiers in oncology · 2023Review
- Review
- Dual contribution of the mTOR pathway and of the metabolism of amino acids in prostate cancer.Cellular oncology (Dordrecht, Netherlands) · 2022Review
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 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTumor cell mediated immune-suppression remains a question of interest in tumor biology. In this study, we focused on the metabolites that are released by prostate cancer cells (PCC), which could potentially attenuate T cell immunity.
methodsProstate cancer cells (PCC) media (PCM) was used to treat T cells, and its impact on T cell signaling was evaluated. The molecular mechanism was further verified in vivo using mouse models. The clinical significance was determined using IHC in human clinical specimens. Liquid chromatography mass spectroscopy (LC/MS-MS) was used to identify the metabolites that are released by PCC, which trigger T cells inactivation.
resultsPCM inhibits T cells proliferation and impairs their ability to produce inflammatory cytokines. PCM decreases ATP production and increases ROS production in T cells by inhibiting complex III of the electron transport chain. We further show that SHP1 as the key molecule that is upregulated in T cells in response to PCM, inhibition of which reverses the phenotype induced by PCM. Using metabolomics analysis, we identified 1-pyrroline-5-carboxylate (P5C) as a vital molecule that is released by PCC. P5C is responsible for suppressing T cells signaling by increasing ROS and SHP1, and decreasing cytokines and ATP production. We confirmed these findings in vivo, which revealed changed proline dehydrogenase (PRODH) expression in tumor tissues, which in turn influences tumor growth and T cell infiltration.
conclusionsOur study uncovered a key immunosuppressive axis, which is triggered by PRODH upregulation in PCa tissues, P5C secretion in media and subsequent SHP1-mediated impairment of T cell signaling and infiltration in PCa.
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.