Continuous stress disrupts immunostimulatory effects of IL-12

► Continuous stress is shown to disrupt the efficacy of immunostimulation with IL-12. ► Both pharmacological and physiological stress paradigms were tested and found deleterious. ► The disruption is evident in NK cell number and activity and lung tumor clearance. ► The stress hormones corticosterone and epinephrine are potential mediators. ► The disruption is more profound in males than in females.