Interleukin-22 promotes PD-L1 expression via STAT3 in colon cancer cells

Xiangpeng Xi1, Rui Hu2, Qi Wang3

  • 1Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong 250014, P.R. China.

Oncology Letters
|August 25, 2021
PubMed

Insights

Interleukin-22 (IL-22) upregulates programmed cell death ligand 1 (PD-L1) in colon cancer. This IL-22/PD-L1 pathway offers a new target for overcoming immune evasion in colon cancer treatment.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Programmed cell death ligand 1 (PD-L1) blockade is a cancer immunotherapy strategy.
  • PD-L1 expression regulation in colon cancer is not fully understood, limiting treatment efficacy.
  • Limited patient benefit from PD-L1 inhibition highlights the need for novel therapeutic targets.

Purpose of the Study:

  • To investigate the role of Interleukin-22 (IL-22) in regulating PD-L1 expression in colon cancer.
  • To elucidate the signaling pathway involved in IL-22-mediated PD-L1 upregulation.
  • To identify new strategies for overcoming immune tolerance in colon cancer.

Main Methods:

  • Analysis of PD-L1 and IL-22 expression in colon cancer tissues.
  • Correlation analysis between IL-22 and PD-L1 expression levels.
  • In vitro experiments using colon cancer cell lines (DLD-1 and primary cells) to assess IL-22 effects on PD-L1.
  • Investigation of the signal transducer and activator of transcription 3 (STAT3) signaling pathway.

Main Results:

  • Both IL-22 and PD-L1 were found to be upregulated in colon cancer tissues.
  • A positive correlation was observed between IL-22 and PD-L1 expression.
  • Exogenous IL-22 treatment increased PD-L1 expression in colon cancer cells.
  • IL-22 upregulated PD-L1 expression through the STAT3 signaling pathway.

Conclusions:

  • IL-22 is a novel regulator of PD-L1 expression in colon cancer.
  • The IL-22/STAT3 pathway contributes to immune evasion in colon cancer.
  • Targeting IL-22 may represent a therapeutic strategy to enhance anti-tumor immunity in colon cancer.

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