Impact of acute influenza infection in lung tumor progression and the tumor microenvironment

The lung tumor microenvironment is highly heterogeneous, and can be shaped by extrinsic factors, including microorganisms. Although lung cancer patients are likely to suffer influenza A virus (IAV) infection during the course of their disease, the impact of acute IAV on lung tumor progression and anti-tumor immune response is largely unexplored. By using a murine model of genetically-induced Kras and p53-mutated lung tumors, our study has provided evidence that acute IAV infection accelerates tumor progression. IAV impairs the generation of tumor-specific T cell responses and leads to the exhaustion of tumor-specific tissue-resident memory CD8+ T cells as well as PD-L1 expression on tumor cells. Furthermore, acute IAV infection induces a specific transcriptional profile which is associated with immunosuppression and modified lipid and drug metabolism. Consistently, this transcriptional IAV-induced signature is found in a subgroup of lung adenocarcinoma patients, in which it is correlated with a poor overall survival. Together, our results reveal that viral infection worsen lung tumor progression by reprogramming the tumor microenvironment towards a more aggressive one, and strongly encourage vaccination of cancer patients against respiratory viral pathogens such as IAV.