{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T12:55:21Z","timestamp":1788267321897,"version":"build-2803163510"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Melatonin, once relegated to the circadian periphery, has resurfaced as a pleiotropic immunomodulator capable of quelling neurogenic inflammation while invigorating antitumour defence. Migraine\u2014and its disabling, episodic neurovascular pain\u2014shares an \u201cinflammatory genome\u201d, defined here as a conserved danger-response gene set (NF-\u03baB, NLRP3, IL1B, NOS2), with the metabolic chaos that subdues cytotoxic immunity in solid cancers; both ignite NF-\u03baB, NLRP3 and reactive-oxygen cascades that erode tissue homeostasis. Emerging evidence shows that endogenous melatonin declines precede migraine attacks, and nightly supplementation rivals first-line preventives in shrinking monthly headache burden while restoring sleep architecture. In parallel, supraphysiological pulses re-programme tumour-associated macrophages toward an iNOS-rich M1 phenotype, amplify granzyme-B output from CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells and down-tune PD-L1 expression on malignant and myeloid cells, thereby widening the therapeutic window of immune-checkpoint blockade. The same cytokines suffused during a migraine flare\u2014IL-6, TNF-\u03b1, ROS\u2014subvert antitumour surveillance; melatonin extinguishes these mediators, synchronises clock-gene\u2013driven metabolism and stitches a biochemical thread between headache relief and cancer immunity. Nanocarrier formulations, chronobiology-guided dosing and rational combinations with CGRP inhibitors or PD-(L)1 antibodies are already advancing through translational pipelines. This review distils molecular pharmacology, pre-clinical models and early-phase trials to portray melatonin as a single, evolutionarily conserved molecule that orchestrates bilateral protection across nervous and oncologic frontiers. By integrating chronotherapy, immunology and neurovascular biology, we aim to identify diagnostic blind spots, repurpose therapeutics and chart a roadmap toward precision strategies that simultaneously alleviate migraine disability and fortify antitumour immunity.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2025.1644066","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T05:31:10Z","timestamp":1753680670000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Melatonin as an anti-inflammatory hormone bridging migraine relief and cancer immunity enhancement: a literature 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