Abstract

Introduction: Smoking is the main risk factor for the development of lung cancer and chronic obstructive lung disease (COPD). Lungs of smokers and COPD patients are frequently colonized with bacterial pathogens. The epithelial cytokine IL-17C mediates the expression of proinflammatory cytokines and chemokines. Therefore, we characterized the function of IL-17C in a preclinical mouse model of tumor growth.

Methods: Lewis lung carcinoma (LLC) cells were injected to initiate the growth of tumors in the lungs of wild-type (WT) mice and mice deficient for IL-17C. Mice were exposed to air or cigarette smoke (CS) in combination with and without exposure to inactivated nontypeable Haemophilus influenzae (NTHi) 7 days after the LLC injection for additional 7 days.

Results: Tumor proliferation and growth were significantly decreased in IL-17C deficient mice exposed to NTHi and CS/NTHi compared to WT mice. Numbers of neutrophils and TNF-α expression were significantly decreased in tumor tissue of IL-17C deficient mice. IL-17C significantly increased the expression of the neutrophil recruiting cytokines KC and MIP-2 in LLC cells in vitro.

Conclusion: Our data indicate that IL-17C regulates the tumor microenvironment, including the recruitment of tumor-associated neutrophils, and tumor growth in inflamed airways.