The melanoma tumor glyco-code impacts human dendritic cells' functionality and dictates clinical outcomes.

Autor:	Sosa Cuevas E; Institute for Advanced Biosciences, Team: Epigenetics, Immunity, Metabolism, Cell Signaling and Cancer, Inserm U 1209, CNRS UMR 5309, Université Grenoble Alpes, Grenoble, France.; Etablissement Français du Sang Auvergne-Rhône-Alpes, R&D Laboratory, Grenoble, France., Roubinet B; GLYcoDiag, Orléans, France., Mouret S; Dermatology, Allergology and Photobiology Department, CHU Grenoble Alpes, Grenoble, France., Thépaut M; Université Grenoble Alpes, CNRS, CEA, Institut de Biologie Structurale, Grenoble, France., de Fraipont F; Medical Unit of Molecular Genetic (Hereditary Diseases and Oncology), Grenoble University Hospital, Grenoble, France., Charles J; Dermatology, Allergology and Photobiology Department, CHU Grenoble Alpes, Grenoble, France., Fieschi F; Université Grenoble Alpes, CNRS, CEA, Institut de Biologie Structurale, Grenoble, France.; Institut Universitaire de France (IUF), Paris, France., Landemarre L; GLYcoDiag, Orléans, France., Chaperot L; Institute for Advanced Biosciences, Team: Epigenetics, Immunity, Metabolism, Cell Signaling and Cancer, Inserm U 1209, CNRS UMR 5309, Université Grenoble Alpes, Grenoble, France.; Etablissement Français du Sang Auvergne-Rhône-Alpes, R&D Laboratory, Grenoble, France., Aspord C; Institute for Advanced Biosciences, Team: Epigenetics, Immunity, Metabolism, Cell Signaling and Cancer, Inserm U 1209, CNRS UMR 5309, Université Grenoble Alpes, Grenoble, France.; Etablissement Français du Sang Auvergne-Rhône-Alpes, R&D Laboratory, Grenoble, France.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2023 Feb 20; Vol. 14, pp. 1120434. Date of Electronic Publication: 2023 Feb 20 (Print Publication: 2023).
DOI:	10.3389/fimmu.2023.1120434
Abstrakt:	Subversion of immunity is a hallmark of cancer development. Dendritic cells (DCs) are strategic immune cells triggering anti-tumor immune responses, but tumor cells exploit their versatility to subvert their functions. Tumor cells harbor unusual glycosylation patterns, which can be sensed through glycan-binding receptors (lectins) expressed by immune cells that are crucial for DCs to shape and orientate antitumor immunity. Yet, the global tumor glyco-code and its impact on immunity has not been explored in melanoma. To decrypt the potential link between aberrant glycosylation patterns and immune evasion in melanoma, we investigated the melanoma tumor glyco-code through the GLYcoPROFILE™ methodology (lectin arrays), and depicted its impact on patients' clinical outcome and DC subsets' functionality. Specific glycan patterns correlated with clinical outcome of melanoma patients, GlcNAc, NeuAc, TF-Ag and Fuc motifs being associated with poor outcome, whereas Man and Glc residues elicited better survival. Strikingly, tumor cells differentially impacting cytokine production by DCs harbored distinct glyco-profiles. GlcNAc exhibited a negative influence on cDC2s, whereas Fuc and Gal displayed inhibitory impacts on cDC1s and pDCs. We further identified potential booster glycans for cDC1s and pDCs. Targeting specific glycans on melanoma tumor cells restored DCs' functionality. The tumor glyco-code was also linked to the nature of the immune infiltrate. This study unveils the impact of melanoma glycan patterns on immunity, and paves the way for innovative therapeutic options. Glycans/lectins interactions arise as promising immune checkpoints to rescue DCs from tumor' hijacking to reshape antitumor immunity and inhibit immunosuppressive circuits triggered by aberrant tumor glycosylation. Competing Interests: Authors BR and LL were employed by company GLYcoDiag. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Sosa Cuevas, Roubinet, Mouret, Thépaut, de Fraipont, Charles, Fieschi, Landemarre, Chaperot and Aspord.)
Databáze:	MEDLINE
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