Melatonin at the Crossroads of Oxidative Stress, Immunity, and Cancer Therapy

Melatonin, an ancient and conserved indolamine, has always attracted attention for its multifunctional roles in redox balance. More recently, it has been studied in relation to immune regulation and cancer biology. Beyond its well-known circadian function, melatonin modulates oxidative stress by directly scavenging reactive oxygen and nitrogen species and by upregulating antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. At the same time, it exerts wide-ranging immunomodulatory functions by influencing both the innate and adaptive immune responses. All these actions converge in the tumor microenvironment, where oxidative stress and immune suppression drive cancer progression. Notably, melatonin influences macrophage polarization, favoring antitumor M1 phenotypes over pro-tumoral M2 states, while attenuating chronic inflammation and restoring mitochondrial function. This review summarizes current knowledge on melatonin’s antioxidant and immunoregulatory mechanisms, highlighting its impact on the tumor immune microenvironment and its potential use as an adjuvant in cancer prevention and treatment.