Acute Influenza Infection Promotes Lung Tumor Growth by Reprogramming the Tumor Microenvironment

One billion people worldwide get flu every year, including patients with non-small cell lung cancer (NSCLC). However, the impact of acute influenza A virus (IAV) infection on the compo-sition of the tumor microenvironment (TME) and the clinical outcome of patients with NSCLC is largely unknown. We set out to understand how IAV load impacts cancer growth and modifies cellular and molecular players in the TME. Herein, we report that IAV can infect both tumor and immune cells, resulting in a long-term protumoral effect in tumor-bearing mice. Mechanis-tically, IAV impaired tumor-specific T-cell responses, led to the exhaustion of memory CD8 thorn T cells and induced PD-L1 expres-sion on tumor cells. IAV infection modulated the transcriptomic profile of the TME, fine-tuning it toward immunosuppression, carcinogenesis, and lipid and drug metabolism. Consistent with these data, the transcriptional module induced by IAV infection in tumor cells in tumor-bearing mice was also found in human patients with lung adenocarcinoma and correlated with poor overall survival. In conclusion, we found that IAV infection worsened lung tumor progression by reprogramming the TME toward a more aggressive state.

Automated summary

We found that acute influenza A virus infection has a significant impact on the tumor microenvironment and clinical outcomes of patients with non-small cell lung cancer. Influenza virus can infect both tumor and immune cells, resulting in long-term protumoral effects. Infection with influenza virus alters the transcriptional profile of the tumor microenvironment and is associated with poor survival in patients with lung adenocarcinoma.