Tumor-Induced Immunosuppression Promotes Brain Metastasis in Patients with Non-Small Cell Lung Cancer

Brain metastases are a devastating, late-stage complication of lung cancer. For metastases to thrive in distant tissue, a favorable niche must exist which includes innate immune cells. Many cancers have the potential to induce systemic immunosuppression, promoting tumor progression. Recent clinical trials of immunotherapy have shown favorable outcomes for patients with late stage lung cancer. However, the role of these agents for early stage disease to prevent metastasis remains unclear. We provide preliminary evidence demonstrating 1) primary brain malignancies induce PD-L1 expression on myeloid cells, resulting in systemic immunosuppression and decreased overall survival, 2) lung cancer patients with brain metastases have increased PD-L1 expression on circulating myeloid cells, and 3) lung cancer brain-metastatic tumors produce soluble factors that can induce PD-L1 on naïve monocytes. Based on these data, we hypothesize that lung cancer induces systemic immunosuppression during progression, allowing for formation of distant metastases in the brain. Identification of these suppressive factors is critical as predictive biomarkers in patients at risk for metastasis and as new therapeutic targets. In this study, we will identify differences in peripheral immune phenotype between non-small cell lung cancer patients with and without brain metastases and investigate the role of tumor-derived cytokines on peripheral immunity. Methods for this study will include ELISA, immunohistochemistry, immunofluorescence staining, flow cytometry, and bioluminescence imaging.