Aspirin’s effect on macrophages beyond its chemopreventive role in inflammation and cancer

Aspirin's antineoplastic activities are primarily executed by irreversibly prohibiting COX-1 in platelets, hindering platelet activation and the subsequent release of compounds that promote tumor development and metastasis. Activated platelets may enhance cancer cells' metastatic potential via direct interaction and/or the release of soluble mediators by inducing COX-2 overexpression. Aspirin's chemopreventive effects may be mediated by COX-independent mechanisms, such as suppressing NF-kB and Wnt/β-catenin signaling. On the other hand, aspirin's effects on macrophages include inflammation resolution, cytokine regulation, and increased phagocytosis. Aspirin has a dual action mechanism, inhibiting macrophage-driven inflammation while simultaneously actively encouraging resolution by increasing phagocytic capacity and anti-inflammatory signaling. These effects occur via both dose-dependent and dose-independent routes and may differ between acute and chronic inflammatory conditions. Key factors, such as macrophage infiltration, immunophenotype, and polarization, are required to appropriately evaluate aspirin's effects and assess its role in the progress of inflammatory disorders and cancer.