Chronic Air Pollution Exposure and the Immunomolecular Profile of Lung Cancer: A Regional Cohort Study

Background/Objectives: Air pollution is progressively acknowledged not only as a carcinogenic exposure, but also as a potential modulator of tumor immune activation and molecular heterogeneity in lung cancer. However, integrated analyses combining long-term environmental exposure, molecular biomarkers and immune phenotype remain limited, especially in Eastern European populations. Methods: We conducted a regional retrospective study including patients diagnosed with lung cancer in Constanța County, Romania. Prolonged atmospheric pollution exposure over an average period of 15 years was estimated using historic environmental monitoring data. Tumor samples were assessed for histopathological subtype, PD-L1 expression and EGFR status, while ALK and KRAS alterations were descriptively analyzed because of the limited number of positive cases. Multivariate ordinal and binary logistic regression models and predicted probability analyses were used to evaluate the association between chronic pollution exposure, PD-L1 expression and EGFR positivity. Results: Chronic NO₂ exposure was significantly associated with increased PD-L1 expression (OR = 1.035, p = 0.017), suggesting an association between NO₂ exposure and an immune-related tumor phenotype. Similar trends were observed for PM10, NO and NOx exposures. Exploratory associations were observed between EGFR positivity and carbon monoxide exposure. Conclusions: Chronic atmospheric pollution was associated with differences in the immune and molecular profile of lung cancer. Long-term exposure to selected pollutants was associated with variations in PD-L1 expression and EGFR status, suggesting that environmental factors may contribute to tumor heterogeneity. However, causal relationships cannot be established from this retrospective observational study.