P69.01 The Role of the Pregnancy Associated Protein Glycodelin and Its Influence on the Immune System in Non-Small-Cell Lung Cancer

Abstract

Lung cancer is the leading cause of cancer related death worldwide and the challenge of developing effective therapies especially for advanced stages remains. Novel approaches concentrating on immunotherapies showed a favorable response in lung cancer patients, making this an interesting and promising field for future research. Glycodelin is an immunosuppressive glycoprotein in reproduction and pregnancy maintenance. Interestingly, high expression levels were also observed in different cancer types, e.g. in non-small-cell lung cancer. To investigate whether glycodelin has similar immunomodulatory characteristics in NSCLC, 22 lectins were used to compare the glycosylation pattern of glycodelin secreted by NSCLC tumor cells to immunosuppressive glycodelin A isolated from amniotic fluid. Furthermore, tumor cell line supernatant containing high amounts of glycodelin was used to treat different immune cell lines. Binding assays were performed and possible effects of the treatment have been evaluated using microarray gene expression analyses. To investigate its influence on the efficiency of immunotherapy, glycodelin was measured in the serum of inoperable immunotherapy-treated NSCLC patients (n = 139) and progression-free survival analysis was performed. We were able to show that the glycosylation of glycodelin from NSCLC is highly similar to glycodelin A and especially shares functional sialylation which is crucial for immune system regulation. In addition, we could validate that glycodelin binds to immune cells. The evaluation of microarray gene expression assays shall give hints for immune escape mechanisms induced by glycodelin. In patients, high serum concentrations of glycodelin were associated with a decreased progression-free survival (p = 0.048) of patients receiving an anti-PD-1-/ PD-L1 therapy. In conclusion, we demonstrate that glycodelin is a protein with a high potential of being a novel target in immuno-oncology especially for NSCLC patients.