Immunomodulatory Synthetic Glycocluster Molecule Prevents Melanoma Growth In Vivo.

Autor:	Honkanen M; Institute of Biomedicine and MediCity Research Laboratory, University of Turku, Tykistökatu 6A, Turku, Finland.; Turku Graduate School of Molecular Medicine, University of Turku, Turku, Finland., Narvi E; Institute of Biomedicine and MediCity Research Laboratory, University of Turku, Tykistökatu 6A, Turku, Finland., Ojala VK; Institute of Biomedicine and MediCity Research Laboratory, University of Turku, Tykistökatu 6A, Turku, Finland.; Turku Graduate School of Molecular Medicine, University of Turku, Turku, Finland.; Turku Bioscience Center, University of Turku and Åbo Akademi University, Tykistökatu 6, Turku, Finland., Jokilammi A; Institute of Biomedicine and MediCity Research Laboratory, University of Turku, Tykistökatu 6A, Turku, Finland.; Turku Bioscience Center, University of Turku and Åbo Akademi University, Tykistökatu 6, Turku, Finland., Rantakari P; Turku Bioscience Center, University of Turku and Åbo Akademi University, Tykistökatu 6, Turku, Finland.; InFLAMES Flagship, University of Turku and Åbo Akademi University, Turku, Finland., Kronqvist P; Department of Pathology, University of Turku and Turku University Hospital, Kiinamyllynkatu 10, Turku, Finland., Kähäri VM; Department of Dermatology, University of Turku and Turku University Hospital, Kiinamyllynkatu 4-8, Turku, Finland.; FICANWest Cancer Research Laboratory, University of Turku and Turku University Hospital, Turku, Finland., Veräjänkorva E; Plastic and General Surgery, Turku University Hospital, Kiinamyllynkatu 4-8, Turku, Finland., Kurppa KJ; Institute of Biomedicine and MediCity Research Laboratory, University of Turku, Tykistökatu 6A, Turku, Finland., Rahkila J; Laboratory of Molecular Science and Engineering, Åbo Akademi University, Henrikinkatu 2, Turku, Finland., Ekambaram R; Laboratory of Molecular Science and Engineering, Åbo Akademi University, Henrikinkatu 2, Turku, Finland., Savolainen J; Department of Pulmonary Diseases and Clinical Allergology, University of Turku and Turku University Hospital, Kiinamyllynkatu 4-8, Turku, Finland., Leino R; Laboratory of Molecular Science and Engineering, Åbo Akademi University, Henrikinkatu 2, Turku, Finland., Elenius K; Institute of Biomedicine and MediCity Research Laboratory, University of Turku, Tykistökatu 6A, Turku, Finland.; Turku Bioscience Center, University of Turku and Åbo Akademi University, Tykistökatu 6, Turku, Finland.; Department of Oncology, University of Turku and Turku University Hospital, Kiinamyllynkatu 4-8, Turku, Finland.
Jazyk:	angličtina
Zdroj:	Chembiochem : a European journal of chemical biology [Chembiochem] 2024 Jun 12, pp. e202400264. Date of Electronic Publication: 2024 Jun 12.
DOI:	10.1002/cbic.202400264
Abstrakt:	Triacedimannose (TADM) is a synthetic trivalent acetylated glycocluster and a transmembrane macrophage activator independent of the mannose receptor. TADM induces Th1-type immune responses and suppresses Th2-type cytokines in acute and chronic allergic inflammation models in vivo. We, therefore, wanted to test whether TADM could also facilitate anti-tumour tissue responses similar to what has been observed for the immune checkpoint inhibitors, such as anti-PD-1 and anti-CTLA-4. A syngeneic mouse melanoma model was selected since metastatic melanoma has been successfully targeted by checkpoint inhibitors in the clinic. TADM inhibited the growth of B16 mouse melanoma tumours at levels comparable to an anti-PD-1 antibody. TADM-treated tumours encompassed significantly more apoptotic cells as measured by TUNEL staining, and interferon-gamma (IFN-γ) expression was increased in the spleens of TADM-treated mice compared to untreated controls. TADM-treated mice also demonstrated increased Ly6 C low monocytes and neutrophils in the spleens. However, TADM-treated tumours showed no discernible differences in infiltrating immune cells. TADM can alone suppress the growth of melanoma tumours. TADM likely activates M1 type macrophages, type N1 neutrophils, and CD8+ and Th1 T cells, suppressing the type 2 immune response milieu of melanoma tumour with a strong type 1 immune response. (© 2024 The Authors. ChemBioChem published by Wiley-VCH GmbH.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu Plný text