Tumor-Microenviroment

Our projects focus on two aspects of multiple myeloma:

(A) the efficient killing of the tumor cells by new substances and through blockade of survival pathways and
(B) the re-activation of the immune system of the patients in order to facilitate immuno-therapy.

Multiple Myeloma (MM) is a clonal B-cell neoplasm that affects terminally differentiated B cells (i.e. plasma cells). The disease is progressive and always lethal and is characterized by the slow proliferation of malignant plasma cells almost exclusively in the bone marrow. Disease manifestations include high levels of monoclonal Igs, immune suppression, and severe skeletal abnormalities resulting from activation of osteoclasts and bone resorption..
(Fig: myeloma cells, mitochondria in red, cell membrane proteins in green)

(A) Killing of myeloma cells

In this project we want to discover new ways to induce apoptosis in these tumor cells and to stop disease progression more efficiently. Therefore we test new substances (natural
compounds in collaboration with the Institut of Pharmacognosie/ University of Innsbruck) as well as inhibitors of important survival pathways (AKT/PKB-Inhibitors) of myeloma cells for their ability to induce apoptosis in the tumor cells. We combine these substances with already utilized chemotherapeutics in order to circumvent known chemo-resistances of the tumor cells.(See Fig: AKT/PKB-pathway)

(B) Immunotherapy in myeloma: enhancing the competence of immune cells

Immunotherapy is a method that holds great promises in the fight against cancer. However, the application is hampered by several factors amongst them the known suppression of the immune system which is seen in many patients suffering from divers tumors. This is also the case in multiple myeloma: the activity of cells of the immune system is suppressed as well as there is a downregulation of the numbers of effective cells. Chemokines are a group of cytokines that have been shown to be mainly involved in the directed migration of cells but evidence is emerging that they might play even more important roles in the progression of tumors. Some members of this protein family were found to contribute to tumor proliferation as well as to the suppression of the immune system. In our project we want to dissect the involvement of myeloma-produced chemokines in the interplay between tumor cells and cells of the immune system such as T-cells and dendritic cells. Whether and how myeloma-derived chemokines are supporting tumor progression and how blocking of these chemokines interferes with disease progression is a main topic our lab and might be utilized in the development of more efficient immunotherapeutic strategies.