Total serum N-glycans associate with response to immune checkpoint inhibition therapy and survival in patients with advanced melanoma

Alessia Visconti, Niccolò Rossi, Helena Deriš, Karla A Lee, Maja Hanić, Irena Trbojević-Akmačić, Andrew M Thomas, Laura A Bolte, Johannes R Björk, Jahlisa S Hooiveld-Noeken, Ruth Board, Mark Harland, Julia Newton-Bishop, Mark Harries, Joseph J Sacco, Paul Lorigan, Heather M Shaw, Elisabeth G E de Vries, Rudolf S N Fehrmann, Rinse K WeersmaTim D Spector, Paul Nathan, Geke A P Hospers, Peter Sasieni, Veronique Bataille, Gordan Lauc, Mario Falchi

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of melanoma and other cancers. However, no reliable biomarker of survival or response has entered the clinic to identify those patients with melanoma who are most likely to benefit from ICIs. Glycosylation affects proteins and lipids' structure and functions. Tumours are characterized by aberrant glycosylation which may contribute to their progression and hinder an effective antitumour immune response.

METHODS: We aim at identifying novel glyco-markers of response and survival by leveraging the N-glycome of total serum proteins collected in 88 ICI-naive patients with advanced melanoma from two European countries. Samples were collected before and during ICI treatment.

RESULTS: We observe that responders to ICIs present with a pre-treatment N-glycome profile significantly shifted towards higher abundancy of low-branched structures containing lower abundances of antennary fucose, and that this profile is positively associated with survival and a better predictor of response than clinical variables alone.

CONCLUSION: While changes in serum protein glycosylation have been previously implicated in a pro-metastatic melanoma behaviour, we show here that they are also associated with response to ICI, opening new avenues for the stratification of patients and the design of adjunct therapies aiming at improving immune response.

Original languageEnglish
Article number166
Pages (from-to)166
JournalBMC Cancer
Issue number1
Publication statusPublished - 18 Feb 2023


  • Humans
  • Immune Checkpoint Inhibitors
  • Melanoma/drug therapy
  • Ambulatory Care Facilities
  • Europe
  • Polysaccharides


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