Interestingly, we proved that both in vitro hypoxic conditions and HIF-1α shuttled from COPD-EVs to recipient cells induce aggressive cancer phenotype and malignant progression through the increase of MICs population, but only in the context of an already activated genetic background of epithelial cells carrying different oncogenic hits, including amplification of KRASV12. The gene discussed is HIF1A; the disease is cancer.