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Galectin-9 Triggers Neutrophil-Mediated Anticancer Immunity

Department of Hematology, University Medical Center Groningen (UMCG), University of Groningen, 9713 GZ Groningen, The Netherlands
Department of Immunology, Kagawa University, Takamatsu, Kagawa 760-0016, Japan
Authors to whom correspondence should be addressed.
These authors contributed equally.
Academic Editor: Galina F. Sud’ina
Biomedicines 2022, 10(1), 66;
Received: 30 November 2021 / Revised: 22 December 2021 / Accepted: 24 December 2021 / Published: 29 December 2021
(This article belongs to the Special Issue Neutrophils, Fast and Strong)
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. View Full-Text
Keywords: carcinoma; galectin-9; neutrophils; trogocytosis; CD47 carcinoma; galectin-9; neutrophils; trogocytosis; CD47
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MDPI and ACS Style

Ustyanovska Avtenyuk, N.; Choukrani, G.; Ammatuna, E.; Niki, T.; Cendrowicz, E.; Lourens, H.J.; Huls, G.; Wiersma, V.R.; Bremer, E. Galectin-9 Triggers Neutrophil-Mediated Anticancer Immunity. Biomedicines 2022, 10, 66.

AMA Style

Ustyanovska Avtenyuk N, Choukrani G, Ammatuna E, Niki T, Cendrowicz E, Lourens HJ, Huls G, Wiersma VR, Bremer E. Galectin-9 Triggers Neutrophil-Mediated Anticancer Immunity. Biomedicines. 2022; 10(1):66.

Chicago/Turabian Style

Ustyanovska Avtenyuk, Natasha, Ghizlane Choukrani, Emanuele Ammatuna, Toshiro Niki, Ewa Cendrowicz, Harm J. Lourens, Gerwin Huls, Valerie R. Wiersma, and Edwin Bremer. 2022. "Galectin-9 Triggers Neutrophil-Mediated Anticancer Immunity" Biomedicines 10, no. 1: 66.

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