Antitumor effects of anti-CD4-depleting antibody in lung fibrosis through CD8+ T cell activation and regulatory T cell inhibition in mice
Background Lung cancer (LC) as a complication worsens the prognosis of patients with idiopathic pulmonary fibrosis (IPF); however, the underlying mechanisms are not fully understood. This study aimed to investigate the immunological characteristics of IPF-LC. Methods We created a murine IPF-LC complication model by intravenous administration of Lewis lung carcinoma cells into bleomycin-induced pulmonary fibrosis model mice. We administered anti-CD4 monoclonal antibody (mAb) to the mice and evaluated the effects on tumor growth, T-cell phenotype in the lungs and lymph nodes, and survival rate. T-cell phenotype was analyzed by flow cytometry and survival analysis was performed using the Kaplan-Meier method. Results Tumor number and size were both significantly increased in this model. CD8+ T cells were significantly decreased, while regulatory T cells (Tregs) were significantly increased in the lungs and lymph nodes. Anti-CD4 mAb treatment significantly increased the number and antitumor gene expression of CD8+ T cells, suppressed tumor growth in fibrotic lungs, reduced the number of Tregs, and improved survival. Conclusions These results indicate that anti-CD4 mAb treatment inhibits tumor growth by enhancing the number and antitumor activity of CD8+ T cells in IPF-LC mice. Anti-CD4 mAb may thus be a promising clinical therapeutic option in patients with IPF-LC. Overall design: RNA-seq profiling of CD8+ T cells from CD4+ Tcell-depleted/control IPF-LC/LC mice