Epigenetic imprinting bridges infection and lung cancer

Abstract The COVID-19 pandemic has highlighted the long-term impact of viral infections on health, yet the impact of SARS-CoV-2 infection on lung cancer development has remained unclear. In a recent study published in Cell, Qian, Wei and colleagues describe an increased risk for the development of lung cancer in patients who suffered from past severe COVID-19. To dissect the mechanisms underlying the epidemiologic evidence, the authors used multiple murine cancer models to demonstrate that respiratory infections, including flu and SARS-CoV-2 infections, remodel the lung tissue microenvironment, leading to an accumulation of neutrophils and immunosuppressive cytokines that promote and sustain a tumor-prone environment. Tumors from previously infected mice contained not only increased numbers of pro-tumorigenic neutrophils but also CD8+ T cells that showed more pronounced signs of immune exhaustion. SARS-CoV-2 vaccination reduced the increase in cancer growth, and blocking neutrophil infiltration combined with immune checkpoint blockade reversed the increase in lung tumor burden. This study demonstrates a long-term molecular memory, or epigenetic imprinting, induced by viral infections in both epithelial and immune cells that can accelerate oncogenesis, and highlights how vaccination protects not only against acute viral infections but also limits the long-term impact of infection on future cancer development.