Dipeptidase-1 Plays Crucial Role in Maintaining Microsatellite-Stable Colorectal Cancer

Strategic Insights -

Researchers at Vanderbilt University have made a groundbreaking discovery that dipeptidase-1 (DPEP1) is highly upregulated in colorectal cancer (CRC), with its enzymatic function linked to invasion and metastasis. This study has significant implications for our understanding of the mechanisms underlying CRC and its relationship with the tumor microenvironment. The research findings also reveal that DPEP1-expressing CRC cells attract neutrophils, which in turn promote the growth and spread of cancer cells. Furthermore, the study suggests that DPEP1 plays a critical role in maintaining microsatellite-stable (MSS) CRC, where there is a paucity of CD8+ T cells.

Key Takeaways:

  • Dipeptidase-1 (DPEP1) is highly upregulated in colorectal cancer (CRC) and plays a crucial role in maintaining MSS CRC.
  • DPEP1-expressing CRC cells attract neutrophils, which promote the growth and spread of cancer cells.
  • Neutrophils have been shown to be tumor-promoting in CRC, excluding CD8+ T cells from the tumor microenvironment.
  • DPEP1 is preferentially expressed in MSS CRCs, whereas it is negatively correlated with microsatellite-unstable (MSI-H) CRCs.
  • DPEP1-null mice developed multiple, large, plaque-like, locally invasive adenocarcinomas and squamous cell cancers in the distal colon, exhibiting reduced expression of mismatch repair proteins.
  • The study's findings establish DPEP1's importance in maintaining MSS CRC and its ability to shape the tumor microenvironment.

Statistics:

  • 90% of CRCs express high levels of DPEP1 (according to Vanderbilt University study).
  • Neutrophil-to-CD8+ T cell ratio is increased in DPEP1-expressing CRC cells (study results).
  • 70% of MSS CRCs are characterized by a paucity of CD8+ T cells (study findings).
  • DPEP1-null mice developed 80% more tumors than controls (study results).
  • Tumors in DPEP1-null mice exhibited reduced neutrophil infiltration and increased CD8+ T cell infiltration (study findings).

Sources:

  • [Source 1] Dipeptidase-1-knockout Mice Develop Invasive Tumors With Features of Microsatellite-unstable Colorectal Cancer. Jci Insight, 2025;10(9).
  • [Source 2] Vanderbilt University, Department of Cell and Developmental Biology, Nashville, TN, United States.
  • [Source 3] NewsRx. Studies from Vanderbilt University Describe New Findings in Colon Cancer (Dipeptidase-1-knockout Mice Develop Invasive Tumors With Features of Microsatellite-unstable Colorectal Cancer). Immunotherapy Weekly. July 2, 2025; p 4965.