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IGF2BP3-Mediated m6A Modification of OLR1 mRNA Promotes Immune Evasion in CRC via the PI3K/AKT/mTOR Pathway

Wei Chen1

  • 1Department of General Surgery, Hebei PetroChina Central Hospital, Guangyang District, Langfang City, Hebei Province, China.

Journal of Immunotherapy (Hagerstown, Md. : 1997)
|August 13, 2026
PubMed

Insights

The OLR1 gene is upregulated in colorectal cancer (CRC), suppressing CD8+ T-cell function and promoting immune evasion. Targeting the IGF2BP3/OLR1 axis may enhance immunotherapy effectiveness for CRC patients.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Colorectal cancer (CRC) is a major global health concern, with immune evasion hindering effective immunotherapy.
  • The role of OLR1 in the CRC immune microenvironment and its regulatory mechanisms are not well understood.

Purpose of the Study:

  • To investigate the function of OLR1 in the colorectal cancer immune microenvironment.
  • To elucidate the upstream and downstream regulatory mechanisms of OLR1 in CRC.
  • To explore the potential of targeting the IGF2BP3/OLR1 axis for CRC immunotherapy.

Main Methods:

  • Utilized TCGA-COAD dataset for bioinformatics analysis.
  • Performed various functional assays including qRT-PCR, Western blotting, ELISA, CCK-8, CFSE, colony formation, Transwell, and flow cytometry.
  • Employed RIP, RNA pull-down, MeRIP, and actinomycin D assays to investigate molecular mechanisms.

Main Results:

  • OLR1 was found to be upregulated in CRC and negatively correlated with CD8+ T-cell infiltration.
  • OLR1 suppressed CD8+ T-cell function and promoted tumor malignancy, while OLR1 knockdown enhanced anti-tumor activity.
  • IGF2BP3 was identified to stabilize OLR1 mRNA in an m6A modification-dependent manner, activating the PI3K/AKT/mTOR pathway and promoting CRC immune evasion.

Conclusions:

  • The IGF2BP3/OLR1 axis plays a critical role in CRC immune evasion by inhibiting CD8+ T-cell antitumor activity.
  • Targeting the IGF2BP3/OLR1 interaction presents a potential therapeutic strategy for enhancing CRC immunotherapy.
Keywords:
IGF2BP3OLR1PI3K/AKT/mTORcolorectal cancerm6A modification

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