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miR-448 targets IDO1 and regulates CD8+ T cell response in human colon cancer

Qiong Lou1,2, Ruixian Liu1, Xiangling Yang1

  • 1Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China.

Journal for Immunotherapy of Cancer
|August 9, 2019
PubMed
Abstract

Insights

Indoleamine 2,3-dioxygenase 1 (IDO1) suppresses CD8+ T cell responses in colon cancer. MicroRNA-448 (miR-448) enhances these responses by inhibiting IDO1, offering a basis for novel colon cancer immunotherapies.

Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • Indoleamine 2,3-dioxygenase 1 (IDO1) regulates T cell function and immune tolerance.
  • IDO1 is upregulated in various cancers, but its role in colon cancer remains unclear.
  • Investigating microRNA (miRNA) regulation of IDO1 in the colon cancer microenvironment is crucial.

Purpose of the Study:

  • To elucidate the function and regulation of IDO1 in colon cancer.
  • To identify specific miRNAs targeting IDO1 in the colon cancer microenvironment.
  • To determine the therapeutic potential of targeting the IDO1-miRNA axis for colon cancer immunotherapy.

Main Methods:

  • Utilized cell-based assays and transplanted tumor models in mice.
  • Assessed IDO1 expression via immunohistochemistry (IHC) and The Cancer Genome Atlas (TCGA).
  • Screened targeting miRNAs using dual luciferase reporter assays and validated miR-448 function via western blotting (WB) and fluorescence-activated cell sorting (FACS).

Main Results:

  • IDO1 overexpression promoted tumor growth in immunocompetent mice.
  • MicroRNA-448 (miR-448) significantly downregulated IDO1 protein expression.
  • miR-448 suppressed CD8+ T cell apoptosis by inhibiting IDO1 activity.

Conclusions:

  • IDO1 inhibits the CD8+ T cell response in colon cancer.
  • miR-448 acts as a tumor suppressor by enhancing the CD8+ T cell response via IDO1 inhibition.
  • These findings support the development of IDO1-targeting immunotherapies for colon cancer.
Keywords:
CD8Colon cancerIDO1ImmunologyTumor microenvironmentmiR-448

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