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Related Experiment Video

Updated: May 11, 2025

Simultaneous Quantification of Selected Kynurenines Analyzed by Liquid Chromatography-Mass Spectrometry in Medium Collected from Cancer Cell Cultures
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Kynurenine promotes the immune escape of colorectal cancer cells via NAT10-mediated ac4C acetylation of PD-L1.

Zaibiao Wang1, Manman Yin2, Ruhang Zhou3

  • 1Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, PR China; Department of General Surgery, The Affiliated Bozhou Hospital of Anhui Medical University, Bozhou, Anhui, PR China.

Clinics (Sao Paulo, Brazil)
|April 17, 2025
PubMed
Summary
This summary is machine-generated.

Kynurenine promotes colorectal cancer immune escape by enhancing PD-L1 expression through NAT10-mediated acetylation. Inhibiting NAT10 or PD-L1 restores T-cell activity and reduces tumor growth.

Keywords:
Colorectal cancerImmune escapeKynurenineN-acetyltransferase 10N4-acetylcytidine modificationProgrammed death-ligand 1

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Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Colorectal cancer (CRC) progression is influenced by the tumor microenvironment.
  • Immune escape is a critical mechanism in CRC development.
  • The kynurenine pathway's role in CRC immunity requires further elucidation.

Purpose of the Study:

  • To investigate the role of kynurenine in colorectal cancer (CRC).
  • To elucidate the mechanism by which kynurenine influences CRC immune escape.
  • To explore the potential of targeting the kynurenine-NAT10-PD-L1 axis.

Main Methods:

  • Assessed kynurenine levels, T-cell populations (CD3+CD4+, CD3+CD8+), and PD-L1 expression.
  • Analyzed RNA modification (ac4C) and NAT10-PD-L1 interaction using molecular assays.
  • Utilized a xenograft rat model to evaluate in vivo effects.

Main Results:

  • Kynurenine suppressed T-cell activation and promoted immune escape in CRC.
  • Kynurenine enhanced NAT10-mediated ac4C modification, increasing PD-L1 expression.
  • NAT10 inhibition or PD-L1 blockade reversed kynurenine-induced immune suppression and tumor growth.

Conclusions:

  • Kynurenine drives CRC immune escape via NAT10-mediated PD-L1 acetylation.
  • Targeting the NAT10-PD-L1 pathway offers a potential therapeutic strategy for CRC.