IMR Press / FBE / Volume 4 / Issue 3 / DOI: 10.2741/E433

Frontiers in Bioscience-Elite (FBE) is published by IMR Press from Volume 13 Issue 2 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article

Fluctuation of systemic immunity in melanoma and implications for timing of therapy

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1 Department of Hematology, Mayo Clinic, Rochester, MN, USA
2 Department of Health Science research, Mayo Clinic, Rochester, MN, USA, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA
3 Department of Medical Oncology, Mayo Clinic, Rochester, MN, USA
4 Department of Medicine University of Melbourne Melbourne, Victoria, Australia, 5Department of Mathematics and Statistics University of Melbourne Parkville, Melbourne, Victoria, Australia
5 College and Alumni Relations, Grinnell College, IA, USA

*Author to whom correspondence should be addressed.

Academic Editor: Luis Porrata

Front. Biosci. (Elite Ed) 2012, 4(3), 958–975; https://doi.org/10.2741/E433
Published: 1 January 2012
(This article belongs to the Special Issue Therapeutic modulation of anti-cancer immunity in humans)
Abstract

Evidence suggests that immunological response in chronic inflammation is dynamic, oscillating between active immunity and tolerance. We hypothesized that a similar dynamic exists in melanoma and administration of therapy during a unique phase of such oscillation could impact clinical outcome. Patients with metastatic melanoma eligible to undergo temozolomide underwent serial measurements of C-reactive protein (CRP) and immune biomarkers every 2-3 days for 2 weeks before starting therapy. Treatment was initiated prior to the estimated next CRP peak, or on day 14 post-registration if a peak was not identified. Time profiles of measured biomarkers were analyzed by fitting serially measured data points to 9 mathematical functions and were correlated to time of therapy and outcome. Data suggested that metastatic melanoma patients exhibit a dynamic immune response. The fluctuation of several biomarkers fitted cosine functions with periods which were multiples of 3-4 days. Chemotherapy delivery during a unique phase of this cycle seemed to correlate with improved response. Individualized conventional chemotherapy delivery by synchronizing treatment with pre-existing patient-specific biorhythms may improve clinical outcomes in metastatic melanoma.

Keywords
Cancer
Biorhythm
Infradian
Inflammation
Oscillation
Dynamics
Cytokines
Immune Cells
Computer Simulation
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