Thymic Stromal Lymphopoietin Induction Suppresses Lung Cancer Development

SIMPLE SUMMARY: The recurrence rate for lung cancer is high after the removal of the primary tumor. Herein, we demonstrate the potential of immunotherapy against lung cancer by examining the impact of Thymic Stromal Lymphopoietin (TSLP) cytokine induction on early lung cancer development. TSLP induction suppresses the development of invasive lung tumors in a mouse model of spontaneous lung cancer. This cancer suppression is dependent on CD4(+) T cells, which highlights the role of adaptive immune response in protection against lung cancer progression. ABSTRACT: Lung cancer is the leading cause of cancer deaths in the United States and across the world. Immunotherapies, which activate tumor-infiltrating cytotoxic T lymphocytes, have demonstrated efficacy for the treatment of advanced-stage lung cancer. However, the potential for harnessing the immune system against the early stages of lung carcinogenesis to prevent cancer development and recurrence remains unexplored. Using a mouse model of lung adenocarcinoma, we investigated the effects of thymic stromal lymphopoietin (TSLP) induction on early cancer development in the lungs. Herein, we demonstrate that systemic TSLP induction suppressed spontaneous lung cancer development in Kras(G12D) mice. TSLP drove a significant CD4(+) T cell response to block lung cancer progression from atypical alveolar hyperplasia to adenocarcinoma. Our findings suggest that TSLP can be used in the early stages of lung cancer development to trigger a lasting immunity in the tissue and prevent the development of advanced disease.