Age-stratified circulating immune signatures reveal non-invasive biomarkers for colorectal cancer detection.

Ageing is a well-recognised factor influencing immune competence; however, elderly individuals remain underrepresented in clinical trials, resulting in gaps in our understanding of their immune responses to disease. To address this gap, we investigated circulating soluble immune checkpoints (sICs) and cytokines in the elderly and middle-aged individuals, both healthy and patients with colorectal cancer (CRC). Our findings revealed a decline in sICs and cytokine levels in healthy elderly individuals compared to their middle-aged counterparts. Key analytes -Galectin-9, sLAG-3, sPD-L1 and sTIM-3- effectively distinguished age groups in healthy volunteers (HVs). However, these differences were not observed when applying this signature in CRC patients, where the combined analysis of plasma Galectin-9, IL-10 and CXCL10 did reliably discriminate between elderly CRC patients and age-matched HVs. This result highlights the potential of these immunological factors as non-invasive biomarkers for cancer detection in this population. In contrast, a much larger number of soluble markers was needed to distinguish CRC patients from HVs among the middle-aged. Collectively, these findings underscore the relevance of observing age stratification for biomarker discovery and lay the groundwork for further exploration of soluble immune mediators in ageing related to tumour pathophysiology.