Inhibition of cellular CDKs by purine analogues revealed that y and o transformed cells differentially respond to the pharmacological CDK inhibitors thereby indicating that overexpression of genes such as p53135Val mutant and oncogenic-Ha-Ras is not able to fully see more override the intrinsic cellular programme. [1] Wesierska-Gadek J, Schmid G. (2000) J Cell Biochem 80:85–103. [2] Schmid G, Kramer MP, Wesierska-Gadek J. (2009) J Cell Physiol 259:459–469. O91 The Role of Myeloma-Derived Chemokine CCL27 on Tumor Progression and Immune Escape Karin Joehrer 1 , Angelika Olivier1, Philipp Ofer1, Daniel Neureiter2, Richard Greil1,3 1 Tyrolean Cancer Research Institute, Innsbruck, Austria, 2 Institute of Pathology at

the Private Medical University Hospital, Salzburg, Austria, 3 Laboratory for Immunological and Molecular Cancer Research and IIIrd Medical Department, University Hospital, Salzburg, Austria www.selleckchem.com/products/jib-04.html multiple myeloma is a still incurable plasma cell tumor and considerable

efforts are undertaken to establish new immunotherapeutic strategies to target this B- cell neoplasm. Chemokines are major players in shaping the tumor microenvironment and can contribute to immune escape of the malignant cells. In the search for important actors of the chemokine network BTK inhibitor in multiple myeloma we found CCL27, which has so far only been correlated with skin diseases such as atopic dermatitis, consistently upregulated in all cell lines investigated. In bone marrow supernatants of tumor patients CCL27

expression correlated with the severity of disease. Myeloma cells were found to express CCR10, the respective receptor, and to be able to utilize the ligand-receptor interaction as an autocrine proliferation loop. Additionally, transendothelial migration of myeloma cells in response to CCL27 was enhanced whereas migration over fibronectin was not affected. We further investigated the impact of CCL27 on immune cells such as T Tau-protein kinase cells and dendritic cells. Dendritic cells differentiated and matured in the presence of CCL27 exhibited a reduced capacity to activate T cells in allogeneic mixed leukocyte reactions. T cell proliferation as well as cytokine production was impaired. Treated dendritic cells showed normal expression of costimulatory molecules but impaired spontaneous migration as well as cytokine production which might explain the impaired T cell function. In coculture experiments with myeloma cell lines, however, these dendritic cells induced enhanced growth of the malignant plasma cells. In summary, we found that CCL27 can modify migration of malignant plasma cells and immune cells. In addition, this chemokine modulates dendritic cells by impairing their potential to activate T cells but, at the same setting, enhances their potential to induce tumor cell growth. Targeting CCL27 therefore could constitute an essential additional component in myeloma therapy.