PMID- 36891308
OWN - NLM
STAT- MEDLINE
DCOM- 20230310
LR  - 20230327
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 14
DP  - 2023
TI  - The melanoma tumor glyco-code impacts human dendritic cells' functionality and 
      dictates clinical outcomes.
PG  - 1120434
LID - 10.3389/fimmu.2023.1120434 [doi]
LID - 1120434
AB  - 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.
CI  - Copyright (c) 2023 Sosa Cuevas, Roubinet, Mouret, Thepaut, de Fraipont, Charles, 
      Fieschi, Landemarre, Chaperot and Aspord.
FAU - Sosa Cuevas, Eleonora
AU  - Sosa Cuevas E
AD  - Institute for Advanced Biosciences, Team: Epigenetics, Immunity, Metabolism, Cell 
      Signaling and Cancer, Inserm U 1209, CNRS UMR 5309, Universite Grenoble Alpes, 
      Grenoble, France.
AD  - Etablissement Francais du Sang Auvergne-Rhone-Alpes, R&D Laboratory, Grenoble, 
      France.
FAU - Roubinet, Benoit
AU  - Roubinet B
AD  - GLYcoDiag, Orleans, France.
FAU - Mouret, Stephane
AU  - Mouret S
AD  - Dermatology, Allergology and Photobiology Department, CHU Grenoble Alpes, 
      Grenoble, France.
FAU - Thepaut, Michel
AU  - Thepaut M
AD  - Universite Grenoble Alpes, CNRS, CEA, Institut de Biologie Structurale, Grenoble, 
      France.
FAU - de Fraipont, Florence
AU  - de Fraipont F
AD  - Medical Unit of Molecular Genetic (Hereditary Diseases and Oncology), Grenoble 
      University Hospital, Grenoble, France.
FAU - Charles, Julie
AU  - Charles J
AD  - Dermatology, Allergology and Photobiology Department, CHU Grenoble Alpes, 
      Grenoble, France.
FAU - Fieschi, Franck
AU  - Fieschi F
AD  - Universite Grenoble Alpes, CNRS, CEA, Institut de Biologie Structurale, Grenoble, 
      France.
AD  - Institut Universitaire de France (IUF), Paris, France.
FAU - Landemarre, Ludovic
AU  - Landemarre L
AD  - GLYcoDiag, Orleans, France.
FAU - Chaperot, Laurence
AU  - Chaperot L
AD  - Institute for Advanced Biosciences, Team: Epigenetics, Immunity, Metabolism, Cell 
      Signaling and Cancer, Inserm U 1209, CNRS UMR 5309, Universite Grenoble Alpes, 
      Grenoble, France.
AD  - Etablissement Francais du Sang Auvergne-Rhone-Alpes, R&D Laboratory, Grenoble, 
      France.
FAU - Aspord, Caroline
AU  - Aspord C
AD  - Institute for Advanced Biosciences, Team: Epigenetics, Immunity, Metabolism, Cell 
      Signaling and Cancer, Inserm U 1209, CNRS UMR 5309, Universite Grenoble Alpes, 
      Grenoble, France.
AD  - Etablissement Francais du Sang Auvergne-Rhone-Alpes, R&D Laboratory, Grenoble, 
      France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230220
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Lectins)
RN  - 0 (Polysaccharides)
SB  - IM
MH  - Male
MH  - Humans
MH  - *Dendritic Cells
MH  - *Melanoma/pathology
MH  - Lectins
MH  - Glycosylation
MH  - Polysaccharides
PMC - PMC9986448
OTO - NOTNLM
OT  - glycan
OT  - human DC subsets
OT  - immune subversion
OT  - lectin
OT  - melanoma
COIS- 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.
EDAT- 2023/03/10 06:00
MHDA- 2023/03/11 06:00
PMCR- 2023/01/01
CRDT- 2023/03/09 02:13
PHST- 2022/12/09 00:00 [received]
PHST- 2023/02/01 00:00 [accepted]
PHST- 2023/03/09 02:13 [entrez]
PHST- 2023/03/10 06:00 [pubmed]
PHST- 2023/03/11 06:00 [medline]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2023.1120434 [doi]
PST - epublish
SO  - Front Immunol. 2023 Feb 20;14:1120434. doi: 10.3389/fimmu.2023.1120434. 
      eCollection 2023.