The role of Chemerin in leukocyte-mediated tumor suppression and immune surveillance.

• Applicant: Dr. Alexander Scholz
• Subject Area: Cell Biology
• Term: from 2013 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 233228468

Cancer is among the most common causes of death in the western civilization. In the past, anti-tumor therapies were solely aiming at destroying malignant transformed cells and still today chemotherapy in combination with radiotherapy is the method of choice. However, solid tumors are more than a bulk of clonal cells but rather represent a mixture of different cell types. Neoplastic lesions are for example highly infiltrated by leukocytes and most frequently by macrophages. While macrophages and other myeloid cells are known to promote tumor progression, effector T-lymphocytes and NK-cells have the capability to control and limit tumor growth. Thus, the transition from malignant transformed cells to larger tumors is strongly regulated by the balance of pro-tumorigenic and anti-tumorigenic leukocytes. It is therefore of great interest to identify proteins that mediate the chemotactic recruitment of immune cells capable of reducing tumor growth. A large microarray database screen could identify chemerin to be significantly downregulated by multiple human and mouse tumors. Chemerin is a chemoattractant that signals via the chemokine-like receptor 1 (CMKLR1), a G protein-coupled receptor that is expressed by NK cells and induces directed cell migration. Initial studies using chemerin overexpressing B16 melanoma cells could show that chemerin is capable of reducing tumor growth in vivo while there was no effect on cultured tumor cells in vitro. This strongly favors the hypothesis that chemerin exerts its anti-tumor effects by the recruitment of NK cells via CMKLR1. Since chemerin injection into established tumors had similar effects, chemerin proves to be a promising candidate for immune-based anti-tumor therapies. Therefore, we aim to further elucidate the role of chemerin in controlling NK-cell recruitment into different tumors and we further want to assess chemerin function in the very early phases of tumor initiation to define its role in tumor immune surveillance.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Eugene C. Butcher