Anti-CD4 monoclonal antibody treatment enhances CD8⁺ T cell antitumor immunity and suppresses tumor growth in pulmonary fibrosis-associated lung cancer in mice

Lung cancer (LC) as a complication worsens the prognosis of patients with idiopathic pulmonary fibrosis (IPF); however, established therapeutic stragegies remain elusive. This study aimed to investigate whether modulation of the immune microenvironment could provide a potential therapeutic strategy in the setting of IPF-associated LC. 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. 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. 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 represent a potential therapeutic option in patients with IPF-LC.