PMID- 36353633 OWN - NLM STAT- MEDLINE DCOM- 20221111 LR - 20221113 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 13 DP - 2022 TI - Unique CLR expression patterns on circulating and tumor-infiltrating DC subsets correlated with clinical outcome in melanoma patients. PG - 1040600 LID - 10.3389/fimmu.2022.1040600 [doi] LID - 1040600 AB - Subversion of immunity by tumors is a crucial step for their development. Dendritic cells (DCs) are strategic immune cells that orchestrate anti-tumor immune responses but display altered functions in cancer. The bases for such DCs' hijacking are not fully understood. Tumor cells harbor unusual glycosylation patterns of surface glycoproteins and glycolipids. DCs express glycan-binding receptors, named C-type lectin receptors (CLR), allowing them to sense changes in glycan signature of their environment, and subsequently trigger a response. Recognition of tumor glycans by CLRs is crucial for DCs to shape antitumor immunity, and decisive in the orientation of the response. Yet the status of the CLR machinery on DCs in cancer, especially melanoma, remained largely unknown. We explored CLR expression patterns on circulating and tumor-infiltrating cDC1s, cDC2s, and pDCs of melanoma patients, assessed their clinical relevance, and further depicted the correlations between CLR expression profiles and DCs' features. For the first time, we highlighted that the CLR repertoire of circulating and tumor-infiltrating cDC1s, cDC2s, and pDCs was strongly perturbed in melanoma patients, with modulation of DCIR, CLEC-12alpha and NKp44 on circulating DCs, and perturbation of Dectin-1, CD206, DEC205, DC-SIGN and CLEC-9alpha on tumor-infiltrating DCs. Furthermore, melanoma tumor cells directly altered CLR expression profiles of healthy DC subsets, and this was associated with specific glycan patterns (Man, Fuc, GlcNAc) that may interact with DCs through CLR molecules. Notably, specific CLR expression profiles on DC subsets correlated with unique DCs' activation status and functionality and were associated with clinical outcome of melanoma patients. Higher proportions of DCIR-, DEC205-, CLEC-12alpha-expressing cDCs were linked with a better survival, whereas elevated proportions of CD206-, Dectin1-expressing cDCs and NKp44-expressing pDCs were associated with a poor outcome. Thus, melanoma tumor may shape DCs' features by exploiting the plasticity of the CLR machinery. Our study revealed that melanoma manipulates CLR pathways to hijack DC subsets and escape from immune control. It further paved the way to exploit glycan-lectin interactions for the design of innovative therapeutic strategies, which exploit DCs' potentialities while avoiding hijacking by tumor, to properly reshape anti-tumor immunity by manipulating the CLR machinery. CI - Copyright (c) 2022 Sosa Cuevas, Valladeau-Guilemond, Mouret, Roubinet, de Fraipont, Landemarre, Charles, Bendriss-Vermare, Chaperot and Aspord. FAU - Sosa Cuevas, Eleonora AU - Sosa Cuevas E AD - Etablissement Francais du Sang Auvergne-Rhone-Alpes, R&D Laboratory, Grenoble, France. AD - Institute for Advanced Biosciences, Team: Epigenetics, Immunity, Metabolism, Cell Signaling & Cancer, Inserm U 1209, CNRS UMR 5309, Universite Grenoble Alpes, Grenoble, France. FAU - Valladeau-Guilemond, Jenny AU - Valladeau-Guilemond J AD - Univ Lyon, Universite Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Leon Berard, Centre de Recherche en Cancerologie de Lyon, Lyon, France. FAU - Mouret, Stephane AU - Mouret S AD - Dermatology, Allergology & Photobiology Department, CHU Grenoble Alpes, Grenoble, France. FAU - Roubinet, Benoit AU - Roubinet B AD - GLYcoDiag, Orleans, 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 - Landemarre, Ludovic AU - Landemarre L AD - GLYcoDiag, Orleans, France. FAU - Charles, Julie AU - Charles J AD - Dermatology, Allergology & Photobiology Department, CHU Grenoble Alpes, Grenoble, France. FAU - Bendriss-Vermare, Nathalie AU - Bendriss-Vermare N AD - Univ Lyon, Universite Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Leon Berard, Centre de Recherche en Cancerologie de Lyon, Lyon, France. FAU - Chaperot, Laurence AU - Chaperot L AD - Etablissement Francais du Sang Auvergne-Rhone-Alpes, R&D Laboratory, Grenoble, France. AD - Institute for Advanced Biosciences, Team: Epigenetics, Immunity, Metabolism, Cell Signaling & Cancer, Inserm U 1209, CNRS UMR 5309, Universite Grenoble Alpes, Grenoble, France. FAU - Aspord, Caroline AU - Aspord C AD - Etablissement Francais du Sang Auvergne-Rhone-Alpes, R&D Laboratory, Grenoble, France. AD - Institute for Advanced Biosciences, Team: Epigenetics, Immunity, Metabolism, Cell Signaling & Cancer, Inserm U 1209, CNRS UMR 5309, Universite Grenoble Alpes, Grenoble, France. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20221024 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Lectins, C-Type) RN - 0 (Membrane Glycoproteins) RN - 0 (Polysaccharides) SB - IM MH - Male MH - Humans MH - *Dendritic Cells MH - Lectins, C-Type/metabolism MH - Membrane Glycoproteins/metabolism MH - Polysaccharides MH - *Melanoma/metabolism PMC - PMC9638162 OTO - NOTNLM OT - CLR OT - cDC1s OT - cDC2s OT - glycan OT - human DC subsets OT - immune subversion OT - melanoma OT - pDCs 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- 2022/11/11 06:00 MHDA- 2022/11/15 06:00 PMCR- 2022/01/01 CRDT- 2022/11/10 02:24 PHST- 2022/09/09 00:00 [received] PHST- 2022/10/10 00:00 [accepted] PHST- 2022/11/10 02:24 [entrez] PHST- 2022/11/11 06:00 [pubmed] PHST- 2022/11/15 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2022.1040600 [doi] PST - epublish SO - Front Immunol. 2022 Oct 24;13:1040600. doi: 10.3389/fimmu.2022.1040600. eCollection 2022.