Galectin-9 Triggers Neutrophil-Mediated Anticancer Immunity

Natasha Ustyanovska Avtenyuk, Ghizlane Choukrani, Emanuele Ammatuna, Toshiro Niki, Ewa Cendrowicz, Harm Jan Lourens, Gerwin Huls, Valerie R. Wiersma, Edwin Bremer*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)
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Abstract

In earlier studies, galectin-9 (Gal-9) was identified as a multifaceted player in both adaptive and innate immunity. Further, Gal-9 had direct cytotoxic and tumor-selective activity towards cancer cell lines of various origins. In the current study, we identified that treatment with Gal-9 triggered pronounced membrane alterations in cancer cells. Specifically, phosphatidyl serine (PS) was rapidly externalized, and the anti-phagocytic regulator, CD47, was downregulated within minutes. In line with this, treatment of mixed neutrophil/tumor cell cultures with Gal-9 triggered trogocytosis and augmented antibody-dependent cellular phagocytosis of cancer cells. Interestingly, this pro-trogocytic effect was also due to the Gal-9-mediated activation of neutrophils with upregulation of adhesion markers and mobilization of gelatinase, secretory, and specific granules. These activation events were accompanied by a decrease in cancer cell adhesion in mixed cultures of leukocytes and cancer cells. Further, prominent cytotoxicity was detected when leukocytes were mixed with pre-adhered cancer cells, which was abrogated when neutrophils were depleted. Taken together, Gal-9 treatment potently activated neutrophil-mediated anticancer immunity, resulting in the elimination of epithelial cancer cells.

Original languageEnglish
Article number66
Number of pages16
JournalBiomedicines
Volume10
Issue number1
DOIs
Publication statusPublished - Jan-2022

Keywords

  • carcinoma
  • galectin-9
  • neutrophils
  • trogocytosis
  • CD47
  • PROGNOSTIC-FACTOR
  • T-CELLS
  • PHOSPHATIDYLSERINE
  • PHAGOCYTOSIS
  • MACROPHAGES
  • CLEARANCE
  • EXPOSURE
  • SURVIVAL
  • INTEGRIN
  • CANCER

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