Immune checkpoint inhibitors (ICIs) rank among the most effective modern cancer therapies. These antibodies activate the immune system by enabling T cells to recognise and destroy tumour cells. In clear cell renal cell carcinoma (ccRCC)—the most common form of kidney cancer—ICIs play a critical role, particularly when metastases have developed and surgery alone is insufficient.
However, despite their success, ICIs are costly, can cause significant side effects, and do not benefit all patients. Importantly, clinicians currently lack reliable tools to predict which patients with ccRCC will respond to immunotherapy.
Turning Attention from Genes to Sugars
To address this challenge, a research team led by Professor Jan Hinrich Bräsen at Hannover Medical School (MHH) explored an unconventional direction. Instead of focusing on genes or proteins, the team investigated sugar structures, also known as glycans, present on cell surfaces. Their findings were published in Analytica Chimica Acta.
Notably, sugar structures are far more diverse than genetic variations and differ from person to person. Every cell carries a complex “sugar landscape,” yet its functional role in cancer therapy response has remained largely unexplored.
Understanding How ICIs Unmask Tumours
Under normal conditions, immune checkpoints regulate T-cell activity, ensuring that healthy cells remain unharmed. Cancer cells exploit this mechanism by binding to checkpoints and disguising themselves as normal cells. Consequently, the immune system fails to recognise them as threats.
As reported by medicalxpress, ICIs block this deceptive interaction. As a result, tumour cells lose their camouflage and become visible to T cells again. However, this mechanism does not work equally well in all ccRCC patients.
Mapping Sugar Structures with Advanced Technology
To uncover why, researchers analysed kidney tissue using MALDI imaging mass spectrometry, combined with AI-assisted digital microscopy. By mapping sugar distributions in healthy and cancerous kidney tissue, the team created a detailed atlas of kidney glycans. They then compared sugar patterns between responders and non-responders to immunotherapy.
Sugar Biomarkers Predict Treatment Response
Crucially, the study identified two specific N-glycan structures that appeared in higher levels among non-responders. These sugar biomarkers could potentially predict, even before treatment begins, whether a patient will benefit from ICI therapy.
Toward More Personalised Cancer Treatment
According to clinicians at MHH, up to one-third of ccRCC patients do not respond to ICIs. Therefore, using sugar-based biomarkers could spare these patients unnecessary treatment, reduce side effects, and lower costs. Although further validation is required, this research marks an important step toward personalised immunotherapy in kidney cancer.