DOI: 10.12688/f1000research.176828.3 ISSN: 2046-1402

Why Static Biomarkers Often Fall Short: Circadian Immune Coherence as a Missing Dimension in Immunotherapy

Ivan Bivolarski
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Biomarkers such as PD-L1 expression and baseline inflammatory indices help inform cancer immunotherapy, but a single measurement provides limited information about how immune activity changes over time. Research on circadian regulation of immunity raises the question of whether the timing and pattern of these changes could provide additional information. In this Opinion Article, we use the term Circadian Immune Coherence (CIC) to describe a proposed framework for studying the reproducibility of approximately 24-hour immune rhythms and the stability of timing relationships between immune markers. It remains unclear whether these features have clinical value. Studying them would require repeated measurements at suitable intervals, since routine blood tests collected weeks apart cannot establish circadian rhythms. Early studies would need to define reproducible measures, account for influences such as sleep, medication, and treatment, and compare their findings with simpler approaches, including baseline measurements and longitudinal trends. The inconvenience and cost of repeated sampling would also need to be justified. CIC is therefore presented as a hypothesis for investigation. Its measurement, relevance to treatment outcomes, and possible role in guiding immunotherapy remain to be established.

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