@article{5b879e5c1d61456cbc122930e3c47426,
title = "Total serum N-glycans associate with response to immune checkpoint inhibition therapy and survival in patients with advanced melanoma",
abstract = "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.",
keywords = "Humans, Immune Checkpoint Inhibitors, Melanoma/drug therapy, Ambulatory Care Facilities, Europe, Polysaccharides",
author = "Alessia Visconti and Niccol{\`o} Rossi and Helena Deri{\v s} and Lee, {Karla A} and Maja Hani{\'c} and Irena Trbojevi{\'c}-Akma{\v c}i{\'c} and Thomas, {Andrew M} and Bolte, {Laura A} and Bj{\"o}rk, {Johannes R} and Hooiveld-Noeken, {Jahlisa S} and Ruth Board and Mark Harland and Julia Newton-Bishop and Mark Harries and Sacco, {Joseph J} and Paul Lorigan and Shaw, {Heather M} and {de Vries}, {Elisabeth G E} and Fehrmann, {Rudolf S N} and Weersma, {Rinse K} and Spector, {Tim D} and Paul Nathan and Hospers, {Geke A P} and Peter Sasieni and Veronique Bataille and Gordan Lauc and Mario Falchi",
note = "Funding Information: This work was supported by the Seerave Foundation. The work was also supported by a grant from the Hanarth Fonds, the Netherlands (2019N1552) to RSNF; and by the Dutch Cancer Society grant 10034 POINTING to EGEdV. The Leeds group was supported by the MRC grant number MR/MO19012/1. This work was also supported by the European Structural and Investment funding for the {\textquoteleft}Croatian National Centre of Research Excellence in Personalized Healthcare{\textquoteright} (contract #KK.01.1.1.01.0010). Funding Information: The authors would like to acknowledge the Seerave Foundation which funded this work. We also thank Oncobiome and the Institut Gustave Roussy for their involvement and support of our initiative. Lastly, we would like to thank all the patients who selflessly took the time to collect samples for this project. Publisher Copyright: {\textcopyright} 2023, The Author(s).",
year = "2023",
month = feb,
day = "18",
doi = "10.1186/s12885-023-10511-3",
language = "English",
volume = "23",
pages = "166",
journal = "BMC Cancer",
issn = "1471-2407",
publisher = "BioMed Central",
number = "1",
}
