Role of Interleukin-22 in breast and lung cancer metastasis

• Applicant: Professor Dr. Sebastian Kobold
• Subject Area: Hematology, Oncology
• Term: from 2019 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 426715005

Cancer cells interact closely with immune cells throughout their lifetime. From the early stages of cancer development, the immune system is involved in some way. Immune cells can clear the nascent tumor or vice versa promote its growth and development. This axis has been exploited therapeutically with significant success: antibodies releasing the brakes off immune cells (so called T cells) have induced therapeutic benefits in otherwise treatment refractory patients. Soluble factors take a central role in the interaction between cancer and immune cells. These factors can impede but also promote tumor growth and development. Interleukin-22 (IL-22) has been identified as an important pro-tumoral factor. We and others have found that IL-22 is frequently expressed in several cancer entities and if found in sufficient amounts generally associated with a dismal outcome. Similarly, IL-22 has been described to induce cell proliferation and promotion in vitro. We could recently describe the regulation of IL-22 in cancer tissue, where cancer cells directly induce IL-22 from T cells via another cytokine interleukin-1. However, the exact function of IL-22 on cancer progression has so far remained largely unknown and there is a lack of data coming from relevant cancer models to investigate this role. In so far unpublished experiments, we could reveal a selective function of IL-22 on metastasis promotion of lung and breast cancer models. IL-22 seem to act directly on cancer cells expressing the IL-22-receptor to sustain lung seeding of the tumor cells. This application will investigate in different genetic models utilizing imaging techniques the mechanism by which IL-22 selectively promotes metastasis mainly to the lung. We will confirm these findings in spontaneous cancer models. The endpoint of metastasis is clinically of high importance, as most death from cancer, are due to metastasis and not the primary tumor which is in sharp contrast to many research investigations focusing on the primary site. This research will help to identify and validating IL-22 as a promising therapeutic structure for selective influencing of metastasis for cancer treatment.

• DFG Programme: Research Grants