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

BMC Cancer

Research

Andrew M. Thomas¹  Rinse K. Weersma²  Johannes R. Björk²  Laura A. Bolte²  Mark Harries³  Heather M. Shaw⁴  Paul Nathan⁴  Jahlisa S. Hooiveld-Noeken⁵  Rudolf S.N. Fehrmann⁵  Geke A. P. Hospers⁵  Elisabeth G.E. de Vries⁵  Ruth Board⁶  Niccolò Rossi⁷  Tim D. Spector⁷  Mario Falchi⁷  Karla A Lee⁷  Alessia Visconti⁷  Veronique Bataille⁸  Mark Harland⁹  Julia Newton-Bishop⁹  Maja Hanić^1,10  Irena Trbojević-Akmačić^1,10  Helena Deriš^1,10  Gordan Lauc^1,11  Joseph J. Sacco^1,12  Peter Sasieni^1,13  Paul Lorigan^1,14 

[1] CIBIO, University of Trento, Trento, Italy;Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center, Groningen, The Netherlands;Department of Medical Oncology, Guy’s and St Thomas’ NHS Foundation Trust, London, UK;Department of Medical Oncology, Mount Vernon Cancer Centre, Northwood, UK;Department of Medical Oncology, University Medical Center Groningen, Groningen, The Netherlands;Department of Oncology, Lancashire Teaching Hospitals NHS Trust, Chorley, UK;Department of Twins Research & Genetics Epidemiology, King’s College London, London, UK;Department of Twins Research & Genetics Epidemiology, King’s College London, London, UK;Department of Dermatology, Mount Vernon Cancer Centre, Northwood, UK;Department of Dermatology, West Herts NHS Trust, Herts, UK;Division of Haematology and Immunology, Institute of Medical Research at St. James’, University of Leeds, Leeds, UK;Genos Glycoscience Research Laboratory, Zagreb, Croatia;Genos Glycoscience Research Laboratory, Zagreb, Croatia;Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia;Liverpool Clatterbridge Cancer Centre, Liverpool, UK;Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK;School of Cancer and Pharmaceutical Sciences, King’s College London, London, UK;The Christie NHS Foundation Trust, Manchester, UK;

关键词: Melanoma;    Immune checkpoint inhibitors;    N-;    Response;    Survival;   

DOI  :  10.1186/s12885-023-10511-3

 received in 2022-07-14, accepted in 2023-01-04,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundImmune 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.MethodsWe 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.ResultsWe 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.ConclusionWhile 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.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

Fig. 6