Evidence map›Paper›PMID 34199263›Full record

ArticleCancers2021

Glyoxalase-1-Dependent Methylglyoxal Depletion Sustains PD-L1 Expression in Metastatic Prostate Cancer Cells: A Novel Mechanism in Cancer Immunosurveillance Escape and a Potential Novel Target to Overcome PD-L1 Blockade Resistance.

Cinzia Antognelli, Martina Mandarano, Enrico Prosperi, Angelo Sidoni, Vincenzo Nicola Talesa

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.6field-weighted citation impact, top 13% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Dual roles of methylglyoxal in cancer.Frontiers in oncology · 2025
    Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Association betweenFrontiers in endocrinology · 2023
    Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. Effect ofAntioxidants (Basel, Switzerland) · 2021
    Article
  18. Article
  19. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Cinzia AntognelliDepartment of Medicine and Surgery, Bioscience and Medical Embryology Division, University of Perugia, L. Severi Square, 06129 Perugia, Italy.ORCID 0000-0002-8259-680X
Martina MandaranoSection of Anatomic Pathology and Histology, Department of Medicine and Surgery, University of Perugia, L. Severi Square, 06129 Perugia, Italy.ORCID 0000-0001-5019-4825
Enrico ProsperiSection of Anatomic Pathology and Histology, Department of Medicine and Surgery, University of Perugia, L. Severi Square, 06129 Perugia, Italy.
Angelo SidoniSection of Anatomic Pathology and Histology, Department of Medicine and Surgery, University of Perugia, L. Severi Square, 06129 Perugia, Italy.
Vincenzo Nicola TalesaDepartment of Medicine and Surgery, Bioscience and Medical Embryology Division, University of Perugia, L. Severi Square, 06129 Perugia, Italy.
University of Perugia · IT

Funding

Università degli Studi di Perugia RB2019CANT
6 · The paper itself

Abstract

Metastatic prostate cancer (mPCa) is a disease for which to date there is not curative therapy. Even the recent and attractive immunotherapeutic approaches targeting PD-L1, an immune checkpoint protein which helps cancer cells to escape from immunosurveillance, have proved ineffective. A better understanding of the molecular mechanisms contributing to keep an immunosuppressive microenvironment associated with tumor progression and refractoriness to PD-L1 inhibitors is urgently needed. In the present study, by using gene silencing and specific activators or scavengers, we demonstrated, in mPCa cell models, that methylglyoxal (MG), a potent precursor of advanced glycation end products (AGEs), especially 5-hydro-5-methylimidazolone (MG-H1), and its metabolizing enzyme, glyoxalase 1 (Glo1), contribute to maintain an immunosuppressive microenvironment through MG-H1-mediated PD-L1 up-regulation and to promote cancer progression. Moreover, our findings suggest that this novel mechanism might be responsible, at least in part, of mPCa resistance to PD-L1 inhibitors, such as atezolizumab, and that targeting it may sensitize cells to this PD-L1 inhibitor. These findings provide novel insights into the mechanisms of mPCa immunosurveillance escape and help in providing the basis to foster in vivo research toward novel therapeutic strategies for immunotherapy of mPCa.

Indexed as

atezolizumabglyoxalase 1immune check-pointimmunosurveillancemetastatic prostate cancermethylglyoxalMG-H1PD-L1/PD-1

Identifiers

PMID34199263
PMCPMC8232032
OpenAlexW3172691952

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.