Evidence map›Paper›PMID 37467751›Full record

ArticleCell chemical biology2023

Hydroxyproline metabolism enhances IFN-γ-induced PD-L1 expression and inhibits autophagic flux.

Stephan H Spangenberg, Amelia Palermo, Nathalia R Gazaniga, Francisco Martínez-Peña, Carlos Guijas, Emily N Chin, Markus M Rinschen, Philipp N Sander, Bill Webb, Laura E Pereira and 4 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell chemical biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.0field-weighted citation impact, top 23% 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

5 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
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

14 authors at 1 institution in 1 country.

Stephan H SpangenbergDepartment of Chemistry, the Scripps Research Institute, La Jolla, CA 92037, USA.
Amelia PalermoScripps Center for Metabolomics, the Scripps Research Institute, La Jolla, CA 92037, USA; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Nathalia R GazanigaDepartment of Chemistry, the Scripps Research Institute, La Jolla, CA 92037, USA.
Francisco Martínez-PeñaDepartment of Chemistry, the Scripps Research Institute, La Jolla, CA 92037, USA.
Carlos GuijasScripps Center for Metabolomics, the Scripps Research Institute, La Jolla, CA 92037, USA.
Emily N ChinDepartment of Chemistry, the Scripps Research Institute, La Jolla, CA 92037, USA.
Markus M RinschenScripps Center for Metabolomics, the Scripps Research Institute, La Jolla, CA 92037, USA.
Philipp N SanderDepartment of Chemistry, the Scripps Research Institute, La Jolla, CA 92037, USA.
Bill WebbScripps Center for Metabolomics, the Scripps Research Institute, La Jolla, CA 92037, USA.
Laura E PereiraDepartment of Chemistry, the Scripps Research Institute, La Jolla, CA 92037, USA.
Ying JiaDepartment of Chemistry, the Scripps Research Institute, La Jolla, CA 92037, USA.
Lance MeitzDepartment of Chemistry, the Scripps Research Institute, La Jolla, CA 92037, USA.
Gary SiuzdakScripps Center for Metabolomics, the Scripps Research Institute, La Jolla, CA 92037, USA; Department of Integrative Structural and Computational Biology, La Jolla, CA 92037, USA. Electronic address: siuzdak@scripps.edu.
Luke L LairsonDepartment of Chemistry, the Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: llairson@scripps.edu.
Scripps Research Institute · US

Funding

Metabolomics Technologies to Advance Biomedical ResearchR35GM130385 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI GARY E SIUZDAK · 2019 to 2026
$3.9M
Mummichog 3, aligning mass spectrometry data to biological networks - Neutral LossU01CA235493 · NCI · JACKSON LABORATORY · PI LI, SHUZHAO, SIUZDAK, GARY E · 2018 to 2021
$2.0M
NCI NIH HHS U01 CA235493NIGMS NIH HHS R35 GM130385
6 · The paper itself

Abstract

The immune checkpoint protein PD-L1 plays critical roles in both immune system homeostasis and tumor progression. Impaired PD-1/PD-L1 function promotes autoimmunity and PD-L1 expression within tumors promotes immune evasion. If and how changes in metabolism or defined metabolites regulate PD-L1 expression is not fully understood. Here, using a metabolomics activity screening-based approach, we have determined that hydroxyproline (Hyp) significantly and directly enhances adaptive (i.e., IFN-γ-induced) PD-L1 expression in multiple relevant myeloid and cancer cell types. Mechanistic studies reveal that Hyp acts as an inhibitor of autophagic flux, which allows it to regulate this negative feedback mechanism, thereby contributing to its overall effect on PD-L1 expression. Due to its prevalence in fibrotic tumors, these findings suggest that hydroxyproline could contribute to the establishment of an immunosuppressive tumor microenvironment and that Hyp metabolism could be targeted to pharmacologically control PD-L1 expression for the treatment of cancer or autoimmune diseases.

Indexed as

B7-H1 AntigenInterferon-gammaAutophagyCell Line, TumorHumansHydroxyprolineB7-H1 AntigenHydroxyprolineInterferon-gammaautophagycollagenhydroxyprolineimmune checkpoint proteinmetabolomics activity screeningPD-L1phenotypic screening

Identifiers

PMID37467751
PMCPMC11426993
OpenAlexW4384701033

What Socratic holds

Textmetadata
LicenceTDM
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.