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Polysialic acid is upregulated on activated immune cells and negatively regulates anticancer immune activity

Olivia Drummond-Guy1, John Daly1, Angeline Wu1

  • 1Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada.

Frontiers in Oncology
|April 4, 2025
PubMed

Insights

Polysialic acid (polySia) is upregulated on immune cells in breast tumors. Removing polySia enhances the immune system's ability to kill cancer cells, suggesting it's a target for cancer immunotherapy.

Area of Science:

  • Immunology
  • Oncology
  • Glycobiology

Background:

  • Anticancer immune suppression drives tumor growth.
  • Polysialic acid (polySia) is upregulated in breast cancer, but its role in immunity is unclear.
  • Understanding immune cell regulation is key for novel cancer immunotherapies.

Purpose of the Study:

  • To investigate the expression and function of polySia on immune cells in breast cancer.
  • To determine polySia's impact on the anticancer immune response.
  • To explore polySia as a therapeutic target for breast cancer.

Main Methods:

  • Profiling polySia expression on healthy and tumor-infiltrating immune cells from breast cancer patients.
  • Stimulating T-cells and macrophages in vitro to assess polySia upregulation.
  • Analyzing polySia attachment to carrier proteins.
  • Evaluating the effect of polySia removal on cancer cell killing by immune cells.

Main Results:

  • PolySia is expressed on multiple immune cell subsets within the tumor microenvironment.
  • In vitro stimulation upregulates polySia on T-cells and macrophages.
  • PolySia is attached to various proteins on immune cells.
  • Selective polySia removal significantly enhances innate immune cell-mediated killing of breast cancer cells.

Conclusions:

  • PolySia is expressed on immune cells in breast tumors and its expression increases upon immune cell activation.
  • PolySia negatively regulates anticancer immunity.
  • Targeting polySia may represent a novel strategy to potentiate cancer immunotherapy.
Keywords:
B cellsNK cellsT-cellscarbohydratesglycansimmune cellsmacrophagespolysialic acid

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