Related Experiment Video
Updated: Aug 9, 2025
Author Spotlight: Assessing the Potential of Circulating Tumor Cells in Leptomeningeal Disease Research
Published on: March 29, 2024
Total serum N-glycans associate with response to immune checkpoint inhibition therapy and survival in patients with
Alessia Visconti1, Niccolò Rossi1, Helena Deriš2
1Department of Twins Research & Genetics Epidemiology, King's College London, London, UK.
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.
Insights
Researchers identified novel serum N-glycome profiles as potential biomarkers for immune checkpoint inhibitor (ICI) response and survival in advanced melanoma patients. This discovery could improve patient stratification and therapy development.
Area of Science:
- Oncology
- Immunology
- Glycobiology
Background:
- Immune checkpoint inhibitors (ICIs) have transformed cancer therapy, but reliable biomarkers for melanoma patient response and survival are lacking.
- Aberrant glycosylation in tumors can impede effective anti-tumor immune responses and influence disease progression.
Purpose of the Study:
- To identify novel glyco-markers for predicting response and survival in patients with advanced melanoma treated with ICIs.
- To investigate the association between serum N-glycome profiles and clinical outcomes in ICI-naive melanoma patients.
Main Methods:
- Analysis of serum N-glycome profiles from 88 ICI-naive advanced melanoma patients from two European cohorts.
- Collection of samples before and during ICI treatment to correlate glycosylation patterns with treatment response and survival.
Main Results:
- Responders to ICIs exhibited a pre-treatment N-glycome profile characterized by higher abundance of low-branched structures and lower antennary fucose.
- This specific N-glycome profile was positively associated with patient survival and demonstrated superior predictive capability for response compared to clinical variables alone.
Conclusions:
- Serum protein glycosylation changes are linked to melanoma response to ICIs, extending previous findings on their role in metastatic behavior.
- These glyco-markers offer new possibilities for patient stratification and the development of adjunct therapies to enhance anti-tumor immune responses.
