Abstract

Oxidative stress is both a driver and a consequence of dysregulated immunity across cancer and chronic 
inflammatory diseases. Reactive oxygen and nitrogen species (ROS/RNS) shape antigen presentation, cytokine 
networks, and cell death pathways; at pathological levels they derail tolerance, fuel fibrosis, and enable tumor 
immune evasion. This review synthesizes mechanistic links between redox biology and immune balance, spanning 
sentinel pathways (Nrf2/Keap1, NF-κB, STAT3, MAPKs, HIF-1α), immunometabolism (AMPK-mTOR, 
glycolysis–OXPHOS coupling), and microenvironmental cues (hypoxia, ferroptosis, lipid peroxidation). We evaluate 
phytochemical classes such as polyphenols, terpenoids, organosulfur compounds, alkaloids, and lignans as redox
active modulators capable of recalibrating innate and adaptive responses while sparing antimicrobial or anti-tumor 
effector functions. Emphasis is placed on how these agents impact dendritic cell fitness, macrophage polarization, 
T-cell exhaustion, myeloid-derived suppressor cells (MDSCs), and stromal crosstalk. We summarize formulation 
and pharmacokinetic advances (nanoformulations, phytosomes, inhaled/topical delivery), safety and drug–drug 
interaction considerations, and the translational evidence landscape. A pragmatic framework is proposed for 
endotype-guided deployment of phytochemical combinations alongside standard therapies to restore immune 
balance.