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Background: Changes in immune marker levels in the blood could be used to improve the early detection of tumor-associated inflammatory processes. To increase predictiveness and utility in cancer detection, intraindividual long-term stability in cancer-free individuals is critical for biomarker candidates as to facilitate the detection of deviation from the norm.

Methods: We assessed intraindividual long-term stability for 19 immune markers (IL10, IL13, TNFa, CXCL13, MCP-3, MIP-1a, MIP-1b, fractalkine, VEGF, FGF-2, TGFa, sIL2Ra, sIL6R, sVEGF-R2, sTNF-R1, sTNF-R2, sCD23, sCD27, and sCD30) in 304 cancer-free individuals. Repeated blood samples were collected up to 20 years apart. Intraindividual reproducibility was assessed by calculating intraclass correlation coefficients (ICC) using a linear mixed model.

Results: ICCs indicated fair to good reproducibility (ICCs ≥ 0.40 and < 0.75) for 17 of 19 investigated immune markers, including IL10, IL13, TNFa, CXCL13, MCP-3, MIP-1a, MIP-1b, fractalkine, VEGF, FGF-2, TGFa, sIL2Ra, sIL6R, sTNF-R1, sTNF-R2, sCD27, and sCD30. Reproducibility was strong (ICC ≥ 0.75) for sCD23, while reproducibility was poor (ICC < 0.40) for sVEGF-R2. Using a more stringent criterion for reproducibility (ICC ≥ 0.55), we observed either acceptable or better reproducibility for IL10, IL13, CXCL13, MCP-3, MIP-1a, MIP-1b, VEGF, FGF-2, sTNF-R1, sCD23, sCD27, and sCD30.

Conclusions: IL10, IL13, CXCL13, MCP-3, MIP-1a, MIP-1b, VEGF, FGF-2, sTNF-R1, sCD23, sCD27, and sCD30 displayed ICCs consistent with intraindividual long-term stability in cancer-free individuals. Impact: Our data support using these markers in prospective longitudinal studies seeking early cancer detection biomarkers.