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Updated: Nov 21, 2025

Isolation and Characterization of Dendritic Cells and Macrophages from the Mouse Intestine
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Isolation and Characterization of Dendritic Cells and Macrophages from the Mouse Intestine

Published on: May 21, 2012

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Notch-Regulated Dendritic Cells Restrain Inflammation-Associated Colorectal Carcinogenesis

Lei Wang1, Shuiliang Yu1, Ernest R Chan2

  • 1Department of Pathology, Case Western Reserve University, Cleveland, Ohio.

Cancer Immunology Research
|January 14, 2021
PubMed

Insights

Notch2 signaling is crucial for dendritic cell (DC) function in preventing colon cancer. Loss of Notch2 in DCs promotes inflammation-associated cancer development and worsens prognosis in mice and humans.

Area of Science:

  • Immunology
  • Oncology
  • Cell Biology

Background:

  • Conventional dendritic cells (cDCs) are vital for anti-tumor T-cell responses.
  • Notch signaling is often downregulated in colorectal cancers, particularly those with GDP-mannose 4,6-dehydratase (GMDS) mutations.
  • Epithelial Notch/Hes1 signaling is downregulated in colitis-associated colorectal cancer models.

Purpose of the Study:

  • To investigate the role of Notch-regulated DC immune responses in colitis-associated colorectal cancer.
  • To determine the impact of Notch2 deficiency in immune cells and DCs on cancer development.
  • To explore the clinical relevance of Notch2 signaling and cDC1 in human colorectal cancers.

Main Methods:

  • Utilized a mouse model of colitis-associated colorectal cancer.
  • Generated chimeric mice with Notch2 deleted in all blood lineages or specifically in DCs.
  • Analyzed cDC differentiation, CCR7 expression, DC migration, and antigen cross-presentation.
  • Examined the correlation between cDC1, Notch2 signaling, and GMDS mutations in human colorectal cancer tissues.

Main Results:

  • Notch2 deficiency in immune cells or DCs promoted inflammation-associated colon cancer transformation in mice.
  • Notch2 deficiency impaired cDC terminal differentiation, reduced CCR7 expression, and suppressed DC migration and antigen cross-presentation.
  • Transfer of Notch-primed DCs inhibited inflammation-associated dysplasia progression.
  • Human colorectal cancers showed a correlation between infiltrating cDC1 and Notch2 signaling.
  • GMDS-mutant colorectal cancers exhibited decreased CCR7 expression and suppressed cDC1 gene signature.
  • Suppressed cDC1 gene signature expression correlated with poor prognosis in human colorectal cancer.

Conclusions:

  • Notch2 signaling plays a critical role in cDC1-mediated antitumor immunity.
  • Notch2-controlled DCs are essential for restraining inflammation-associated colon cancer development.
  • Notch2 and cDC1 signatures may serve as prognostic markers in human colorectal cancer.

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