Temporal shifts in post-asthmatic immune responses define tumor outcomes via strain-specific monocyte reprogramming

Epidemiological evidence linking asthma to lung cancer risk remains contradictory, presenting asthma as either a risk factor or a protective condition. We hypothesize that this heterogeneity stems from the temporal dynamics of inflammatory response and host genetic background. Using ovalbumin (OVA)-induced asthma models, we identify a temporal shift in immune effectors driving post-asthmatic tumorigenesis. During acute airway inflammation, eosinophil infiltration accelerates tumor growth across mouse strains. Following resolution, however, tumorigenic outcomes in recovery diverge along genetic lines. Prior asthma reshapes chromatin landscapes of bone marrow myeloid progenitors, establishing innate immune memory that differentially programs monocytes across strains. In C57BL/6 mice, trained monocytes adopt oxidative phosphorylation (OXPHOS), acquiring a suppressive, tissue-remodeling phenotype that promotes tumor progression. Conversely, BALB/c-trained monocytes utilize glycolysis to maintain a pro-phagocytic state, enabling tumor clearance. These findings delineate a biphasic mechanism wherein temporal shifts in post-asthmatic immune responses define tumor outcomes via strain-specific monocyte metabolic reprogramming.