Melanoma tumour-derived glycans hijack dendritic cell subsets through C-type lectin receptor binding.

Autor: Niveau C; Institute for Advanced Biosciences, Team: Epigenetics, Immunity, Metabolism, Cell Signaling & Cancer, Inserm U 1209, CNRS UMR 5309, Université Grenoble Alpes, Grenoble, France.; R&D Laboratory, Etablissement Français du Sang Auvergne-Rhône-Alpes, Grenoble, France., Sosa Cuevas E; Institute for Advanced Biosciences, Team: Epigenetics, Immunity, Metabolism, Cell Signaling & Cancer, Inserm U 1209, CNRS UMR 5309, Université Grenoble Alpes, Grenoble, France.; R&D Laboratory, Etablissement Français du Sang Auvergne-Rhône-Alpes, Grenoble, France., Roubinet B; GLYcoDiag, Orléans, France., Pezet M; Institute for Advanced Biosciences, Plateforme de Microscopie Photonique-Imagerie Cellulaire et Cytométrie en Flux (Microcell), Inserm U1209-CNRS UMR 5309, Université Grenoble Alpes, Grenoble, France., Thépaut M; Institut de Biologie Structurale, Université Grenoble Alpes, CNRS, CEA, Grenoble, France., Mouret S; Dermatology, Allergology & Photobiology Department, CHU Grenoble Alpes, Université Grenoble Alpes, Grenoble, France., Charles J; Dermatology, Allergology & Photobiology Department, CHU Grenoble Alpes, Université Grenoble Alpes, Grenoble, France., Fieschi F; Institut de Biologie Structurale, Université Grenoble Alpes, CNRS, CEA, 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 & Cancer, Inserm U 1209, CNRS UMR 5309, Université Grenoble Alpes, Grenoble, France.; R&D Laboratory, Etablissement Français du Sang Auvergne-Rhône-Alpes, Grenoble, France., Saas P; Institute for Advanced Biosciences, Team: Epigenetics, Immunity, Metabolism, Cell Signaling & Cancer, Inserm U 1209, CNRS UMR 5309, Université Grenoble Alpes, Grenoble, France.; R&D Laboratory, Etablissement Français du Sang Auvergne-Rhône-Alpes, Grenoble, France., Aspord C; Institute for Advanced Biosciences, Team: Epigenetics, Immunity, Metabolism, Cell Signaling & Cancer, Inserm U 1209, CNRS UMR 5309, Université Grenoble Alpes, Grenoble, France.; R&D Laboratory, Etablissement Français du Sang Auvergne-Rhône-Alpes, Grenoble, France.
Jazyk: angličtina
Zdroj: Immunology [Immunology] 2024 Feb; Vol. 171 (2), pp. 286-311. Date of Electronic Publication: 2023 Nov 22.
DOI: 10.1111/imm.13717
Abstrakt: Dendritic cell (DC) subsets play a crucial role in shaping anti-tumour immunity. Cancer escapes from the control immune system by hijacking DC functions. Yet, bases for such subversion are only partially understood. Tumour cells display aberrant glycan motifs on surface glycoproteins and glycolipids. Such carbohydrate patterns can be sensed by DCs through C-type lectin receptors (CLRs) that are critical to shape and orientate immune responses. We recently demonstrated that melanoma tumour cells harboured an aberrant 'glyco-code,' and that circulating and tumour-infiltrating DCs from melanoma patients displayed major perturbations in their CLR profiles. To decipher whether melanoma, through aberrant glycan patterns, may exploit CLR pathways to mislead DCs and evade immune control, we explored the impact of glycan motifs aberrantly found in melanoma (neoglycoproteins [NeoGP] functionalised with Gal, Man, GalNAc, s-Tn, fucose [Fuc] and GlcNAc residues) on features of human DC subsets (cDC2s, cDC1s and pDCs). We examined the ability of glycans to bind to purified DCs, and assessed their impact on DC basal properties and functional features using flow cytometry, confocal microscopy and multiplex secreted protein analysis. DC subsets differentially bound and internalised NeoGP depending on the nature of the glycan. Strikingly, Fuc directly remodelled the expression of activation markers and immune checkpoints, as well as the cytokine/chemokine secretion profile of DC subsets. NeoGP interfered with Toll like receptor (TLR)-signalling and pre-conditioned DCs to exhibit an altered response to subsequent TLR stimulation, dampening antitumor mediators while triggering pro-tumoral factors. We further demonstrated that DC subsets can bind NeoGP through CLRs, and identified GalNAc/MGL and s-Tn/ C-type lectin-like receptor 2 (CLEC2) as potential candidates. Moreover, DC dysfunction induced by tumour-associated carbohydrate molecules may be reversed by interfering with the glycan/CLR axis. These findings revealed the glycan/CLR axis as a promising checkpoint to exploit in order to reshape potent antitumor immunity while impeding immunosuppressive pathways triggered by aberrant tumour glycosylation patterns. This may rescue DCs from tumour hijacking and improve clinical success in cancer patients.
(© 2023 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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