Pirfenidone increases immune infiltrate and delays the tumor growth when combined with PD-L1 checkpoint blockade

IPF patients have a high risk to develop lung cancer, with few treatment options available. Immune checkpoint inhibitors (ICIs) are widely used for the treatment of non-small cell lung cancer (NSCLC) in clinical practice, however, the incidents of immune-related pneumonitis are high in patients with both IPF and lung cancer. Pirfenidone (PFD) is an antifibrotic drug which has been approved for the treatment of mild to moderate IPF. In this study, by using murine syngeneic tumor models, we found that PFD induced a T cell inflamed tumor microenvironment and delayed the tumor growth when combined with ICIs. No obvious sign of drug toxicity was observed in mice treated with the combination regimen. By applying an unbiased transcriptomic approach, we found that combination treatment promotes gene expression associated with innate and adaptive immune cells, resulting in infiltration of immune cells and optimal T cell positioning. Our data provide a strong rationale to clinically explore the potential of PFD to enhance anti-tumor immune response, particularly, in lung cancer patients with preexisting IPF.